| Part ?:Study of PI3K/Akt/mTOR pathway pain-promoting mechanism in sciatic nerve endometriosis modelBackground:Endometriosis(EM)has become a common and frequently-occurring disease during childbearing age and about 5-10%of women were influenced by it.The main feature of EM is the endometrial stromal or glandular cells went outside the uterine cavity.Its main pathogenesis is ovary,fallopian tube,and uterine ligament tissue,a few cases also appeared in other parts of the body,such as the pleura,pericardium and even the brain.One of the main symptoms of EM is pain,including dysmenorrhea,chronic pelvic pain,painful intercourse,and even dysuria.Hormone and surgery were the main treatments for EM.However,about 50%patients would feel pain in 5 years after surgery,they could not discover the lesions until the heavy pain.In addition,there is little painkillers for EM.Therefore,it is necessary to find a new and treatment for endometriosisSciatic nerve endometriosis is a rare and special type of deep endometriosis,In addition to pain,sciatic nerve endometriosis is also accompanied by dysfunction of the affected limb.The current treatment are insufficiently understood.At present,the treatments used currently are similar to ordinary endometriosis,including choosing oral contraceptives,GnRH-a,non-steroidal anti-inflammatory drugs and some traditional Chinese medicines.Moreover,some suitable gentle exercises will play a role,such as walking,yoga,swimming,and physical therapy.When the abovementioned treatments do not well work,the ectopic endometrial can be removed by surgery,so as to achieve the purpose of treating or alleviating the pain of sciatic nerve endometriosis.However,the conventional treatments are insufficient to treat the intrauterine ectopic heteropathic disease.For example,although oral contraceptives can help patients relieve pain,it has a higher risk of thromboembolism for patients over 40 years or with have high-risk factors(such as diabetes,hypertension,smoking,history of thrombosis);although GnRH-a can effectively relieve pain,long-term application will cause perimenopausal symptoms such as hypogyny and calcium loss;non-steroidal anti-inflammatory drugs are often effective in the short term.Surgical treatment requires an experienced surgeon with a clearer understanding of the blood vessels,branches of the sciatic nerve and surrounding pelvic region in order to accurately determine the ectopic endometrium.At the same time,it is often accompanied by endometriotic tissue reaching the sciatic nerve foramen or along the nerves and blood vessels to the pelvic opening.Additonally,hysteroscopy is still not easy to be available,and to operate in the back of the pelvis through the buttocks will greatly increase the risk.Pain is the response of the central nervous system to peripheral noxious stimuli.Endometriotic pain is the result of the interaction of central and peripheral factors.The same is true for the pain mechanism of sciatic nerve endometriosis.A deep understanding of the mechanism can help us Find an effective way to treat endometriosis pain.At present,the research on endometriosis pain mainly focuses on the peripheral mechanism,and the research on the central mechanism is rare.The sciatic nerve endometriosis rat model is more suitable for studying the central mechanism of endometriosis pain due to its own characteristics.This experiment established a rat sciatic nerve endometriosis model to simulate the pain symptoms of clinical patients with sciatic nerve endometriosis,so as to explore the central mechanism of endometriosis,especially sciatic nerve endometriosis,and find the treatment of endometriosis based on this.In particular,effective drugs for sciatic nerve endometriosis pain are expected to bring new breakthroughs in the treatment of endometriosis pain.The PI3K/Akt signaling pathway is involved in the occurrence of neuropathic pain and inflammatory pain.Endometriosis is redefined as neuropathic pain due to the formation of nerve endings in the lesion and the distribution of types.The activation of this pathway can induce and maintain hyperalgesia,participate in synaptic plasticity in the center,and participate in the process of pain facilitation after tissue injury in the periphery.PI3K/Akt pathway plays an important role in the formation and development of neuropathic pain,and this signaling pathway directly participates in the protection of ventral motor neurons in a rat model of sciatic nerve injuryLY294002 is an inhibitor of PI3K/Akt pathway.In this study,we tried to explore the PI3K/Akt/mTOR signaling pathway in superficial spinal dorsal horn and the neurotransmitter related to pain released by LY294002 by inhibiting the activation of PI3K/Akt pathway Objective to investigate the role of substance P(SP)and calcitonin gene-related peptide(CGRP)in pain of sciatic nerve endometriosisObjective:In this study,we established a rat model of sciatic nerve endometriosis.Based on the understanding of the pain mechanism of endometriosis,we studied the effect of PI3K/Akt/mTOR signaling pathway on the pain response and the expression of signal pathway proteins,and the potential pain promoting mechanism.Methods:The sciatic nerve endometriosis model(SNEM)was established,and the rats were randomly divided into normal control group(Sham group),endometriosis control group(ENDO+DMSO group),LY294002(inhibitors of PI3K/Akt/mTOR signaling pathway)drug treatment group(ENDO+LY294002 group),with 8 rats in each group.Subarachnoid administration was used.The catheter was connected with Hamilton microinjector,and the local microdose was given according to the appropriate concentration.Later testing1.Von Frey fiber test and thermal pain sensitivity test were used to detect the pain level of sciatic nerve endometriosis model animals2.qPCR and Western blot were used to detect the mRNA and protein phosphorylation levels of PI3K,Akt and mTOR in the superficial layer of spinal dorsal horn around the lesion in Sham group,ENDO+DMSO group and ENDO+LY294002 group.3.qPCR and Western blot were used to detect the mRNA and protein expression levels of SP,CGRP and NGF in the superficial layer of spinal dorsal horn around the lesion in Sham group,ENDO+DMSO group and ENDO+LY294002 group.4.Use graphpad prism 8.0 to analyze the data.The statistical methods include student t-test,univariate analysis of variance,bivariate analysis of variance and Tukey's post test.Results:1.Accompanying PI3K/Akt pathway activation in sciatic nerve endometriosis Compared with the superficial tissues of dorsal horn of spinal cord in Sham group,the mRNA levels of PI3K,Akt and mTOR were significantly increased,and the differences between the two groups were significant(p<0.01).Compared with the ENDO group,the mRNA levels of PI3K,Akt and mTOR were significantly lower in ENDO+LY294002 group(PI3K ENDO+LY294002 vs ENDO:1.33±0.47 vs2.86±0.59,p<0.05;Akt ENDO+LY294002 vs ENDO:2.02±0.52 vs 3.14±0.69,p<0.05;mTOR ENDO+LY294002 vs ENDO:1.64±0.49 vs 3.72±0.89,p<0.01).Compared with the ENDO group,the phosphorylation levels of PI3K,Akt and mTOR were significantly lower in ENDO+LY294002 group(PI3K ENDO+LY294002 vs ENDO:1.24±0.41 vs 2.72±0.54,p<0.05;Akt ENDO+LY294002 vs ENDO:1.72±0.46 vs 3.41±0.67,p<0.05;mTOR ENDO+LY294002 vs ENDO:2.01±0.43 vs 3.13±0.59,p<0.05)2.PI3K/Akt inhibitor improved the dose effect of painful allergies of the intimal endometriosisAt 2,3,4,5 and 6 hours after intrathecal injection of LY294002,the pain tolerance of mechanical stimulation in ENDO+LY294002 group was significantly higher than that of ENDO group(7.0±1.1 vs 3.9±0.9,8.2±.6 vs 3.5±.0,9.0±1.6 vs 3.7±0.9,7.9±2.2 vs 4.0±1.0,7.0±1.9 vs 3.7±0.8,p<0.05);From the third day,the mechanical hyperalgesia of ENDO+LY294002 group was significantly improved than that of ENDO group(8.4±1.9 vs 3.9±1.0,p<0.01).It was significantly higher in ENDO group(12.3±2.5 vs 6.9±2.0,p<0.01)and ENDO+DSMO group(12.3±2.5 vs 6.6±1.9,p<0.01).There was no statistical significance in the mechanical hyperalgesia of hind limb in ENDO group and ENDO+DSMO group at any time point(p>0.05).Compared with ENDO group,ENDO+LY294002 group significantly increased the heat shock tolerance of hind limbs at 3,4,5,6 and 7 hours after treatment(8.2±1.6 vs 3.5±1.0,9.0±1.6 vs 3.7±0.9,7.9±2.2 vs 4.0±1.0,7.0±1.9 vs 3.7±0.8,5.7±1.4 vs 3.9±1.0,p<0.05).From the third day,the hyperalgesia of ENDO+LY294002 group was significantly improved than that of ENDO group(5.98±1.87 vs 2.75±1.06,p<0.01).After 21 days,it was significantly higher than that in ENDO group(10.37±2.53 vs 5.63±2.01,p<0.01)and ENDO+DSMO group(10.37±2.53 vs 5.52±1.88,p<0.01).The thermal hyperalgesia of hind limb in ENDO group and ENDO+DSMO group had no statistical significance at any time point,p>0.05.Injection of the PI3K/Akt inhibitor LY294002 induced by the induction of the apiatic nectar endometriosis,can significantly improve the pain sensitivity of the animal hind limbs;sustained administration can reduce the pain sensitivity of rats to external mechanical stimulation and thermal stimulation.3.Dose effect relationship of PI3K/Akt inhibitor on pain sensitivity in sciatic endometriosisThe model group was given LY294002(5,10,30,50mg/kg)with different concentration gradients.The results showed that when the concentration of the drug was 10mg/kg,the mechanical hypersensitivity and the heat pain allergy were decreased compared with those in the model group due to sciatic neuro endometriosis.The response threshold of the two groups was significantly improved,and there were significant differences(p<0.05).When the concentration of the drug was 10-30mg/kg,the therapeutic effect was dose-dependent.However,there was no significant difference(p>0.05)in pain tolerance between the two groups(30mg/kg and 50mg/kg)Thus,the intervention of LY294002 was set to 30mg/kg in the following study.4.PI3K/Akt/mTOR signaling pathway affects the expression of substance P and calcitonin gene-related peptideThe protein and mRNA expression of substance P and CGRP in the superficial tissue of dorsal horn of spinal cord around the lesions were detected.Compared with sham group,the expressions of substance P and CGRP(444.8±36.1 vs 269.4±26.3pg/ml,p<0.01)in ENDO+DMSO group were significantly higher(SP ENDO+DMSO vs ENDO:297.2±30 vs 176.7±22.3pg/ml,p<0.01;CGRP ENDO+DMSO vs ENDO:444.8±36.1 vs 269.4±26.3pg/ml,p<0.01).The protein expression of substance P and CGRP in ENDO+LY294002 group were lower than those in ENDO+DMSO group(SP ENDO+DMSO vs ENDO:297.2±30 vs 231.1 ±27.3 pg/ml,p<0.01:CGRP ENDO+DMSO vs ENDO:304.8±31.2 vs 444.8±36.1 pg/ml,p<0.05).5.Inhibition of PI3K/Akt/mTOR signaling pathway affects the expression of nerve growth factorLY294002 could inhibit the expression of NGF(1.53±0.23vs1),and the difference was significant(p<0.05).The changes in the protein level of NGF was the same as that of mRNA(2.95±0.51 vs 1.83±0.36),and the difference was significant(p<0.05).The mRNA level of NGF in ENDO+DMSO group was significantly higher than that in sham group(2.05±0.33vs1,p<0.05).The mRNA level of NGF in ENDO+LY294002 group was significantly lower than that in ENDO+DMSO group(ENDO+LY294002 vs ENDO+DMSO:1.53±0.23 vs 2.05±0.33,p<0.05).But it was still significantly higher than that in sham group.The protein level of NGF in ENDO+DMSO group was significantly higher than that in sham group(2.95±0.51vs1,p<0.01).After treatment with LY294002,the protein level of NGF in ENDO+LY294002 group was significantly lower than that in ENDO+DMSO group(ENDO+LY294002 vs ENDO+DMSO:1.83±0.36 vs 2.95±0.51,p<0.05),but still significantly higher than that in sham group.Conclusions:1.PI3K/Akt/mTOR signaling pathway participates in the occurrence and development of pain in sciatic neuropathy.2.PI3K/Akt/mTOR signaling pathway is involved in regulating the pain sensitivity of sciatic nerve endometriosis by promoting downstream substance P,calcitonin gene-related peptide and nerve growth factor3.LY294002 can improve the pain sensitivity of sciatic endometriosis by inhibiting the expression of substance P,calcitonin gene-related peptide and nerve growth factor,which is of great significance to develop a new treatment method for sciatic neuropathyPart II:Study on analgesic mechanism of sulforaphane in sciatic nerve endometriosis modelBackground:Sciatic nerve endometriosis is a type of estrogen-dependent inflammatory disease In patients with endometriosis of the sciatic nerve,ectopic lesions are mostly found around the sciatic nerve,within the sciatic nerve sheath,or near the sciatic tuberosityThe main symptoms of sciatic nerve endometriosis are sciatica and dyskinesia.Because the clinical manifestations of sciatic nerve endometriosis are similar to lumbar disc herniation,it is easy to be misdiagnosed as lumbar disc herniation,leading to delays in the diagnosis and condition of patients.For sciatic nerve endometriosis,current treatments are very limited.For sciatic nerve endometriosis,the normal environment for the growth of the endometrium is in the uterus.Once the ectopic endometrium grows around the sciatic nerve,it will be recognized by the body as a foreign substance,resulting in immune inflammation and immunity Attack,try to clear it.Its treatment is based on surgery and drugs.The operation requires the surgeon to be experienced and familiar with the blood vessels around the sciatic nerve and its branches.The operation risk is relatively high.Drug treatment can choose oral contraceptives,GnRH-a,non-steroidal anti-inflammatory drugs and traditional Chinese medicine,but these treatments have shortcomings.Looking for a natural medicine that can not only inhibit inflammation and relieve pain,but also inhibit the growth of lesions,may have a profound impact on the treatment of endometriosis,especially sciatic nerve endometriosis.Sulforaphane(SFN)is a naturally occurring isothiocyanate in cruciferous vegetables and has been proven to have anti-diabetic,anti-cancer and antibacterial effects.Recently,it has been discovered that sulforaphane has a good anti-inflammatory effect.For example,sulforaphane has been shown to inhibit bacterial lipopolysaccharide-induced inflammation,which is characterized by increasing the expression of TNF-?,IL-1?,inducible nitric oxide synthase(iNOS)and prostaglandin peroxidase synthase 2(COX-2),so as to play a neuroprotective effect.Sulforaphane can also prevent renal fibrosis and ischemia-reperfusion injury by regulating inflammation.In addition,another important application of sulforaphane is to relieve pain.However,despite the potential of sulforaphane in reducing inflammation and pain,there have been no reports of sulforaphane in the treatment of sciatic nerve endometriosisPurposes:This study established the rat sciatic nerve endometriosis model,observed the effect of Sulforaphane on the pain of sciatic nerve endometriosis in three aspects:the volume of the lesion,the pain response and the inflammatory response,and further explored the analgesic mechanism of Sulforaphane in the model of sciatic nerve endometriosisMethods:The sciatic nerve endometriosis(SNEM)model was established,and the experimental rats were randomly divided into sham operation group(Sham group),endometriosis control group(ENDO group),and sulforaphane drug treatment group(ENDO+SFN group)with 6 animals in each group.The sciatic nerve endometriosis model was established as in the first part of the study.After the administration of sulforaphane 5,15,30,60 mg/kg,the changes of pain threshold(PWT)caused by mechanical stimulation and pain threshold(PWL)caused by thermal stimulation were detected.And the optimal concentration of sulforaphane was selected for further study,and then perform the following tests in the Sham group,ENDO group,and ENDO+SFN group.1.Von Frey Fiber Test and Thermal Pain Sensitivity Test were used to determine the pain threshold of mechanical stimulation(PWT)and the pain threshold of thermal stimulation(PWL)2.ELISA and Western blot were used to detect the VEGF expression in the lesion area of rats in Sham,ENDO,ENDO+SFN groups.3.ELISA and qPCR were used to detect the expression of inflammatory cytokines IL-6,IL-1?,TNF-? protein and mRNA in the superficial spinal dorsal horn of rats in the Sham,ENDO,ENDO+SFN groups4.qPCR and western blot were used to detect the expression of iNOS,COX-2 protein and mRNA in the superficial spinal dorsal horn of rats in the Sham,ENDO,ENDO+SFN groups.5.Western blot were used to detect the expression of Keap1 and Nrf2 in the superficial tissues of the spinal dorsal horn in the Sham,ENDO,ENDO+SFN groupsResults:1.Sulforaphane can significantly improve the hyperalgesia of sciatic nerve endometriosisBefore modeling,the baseline pain levels of the three groups of rats were the same;in the ENDO+SFN group,the test on the 7th day showed that the hyperalgesia caused by mechanical stimulation and the hyperalgesia caused by thermal stimulation were improved compared with the ENDO group(mechanical hyperalgesia ENDO+SFN vs ENDO:1 1.4±2.1 vs 7.2±1.7,p<0.01;thermal hyperalgesia ENDO+SFN vs ENDO:6.4±1.1 vs 3.2±1.7,p<0.01),ENDO+SFN group,the 14th day test showed mechanical stimulation Hyperalgesia caused by hyperalgesia and thermal stimulation was better than ENDO group(mechanical hyperalgesia ENDO+SFN vs ENDO:10.8±2.0 vs 5.7±1.9,p<0.01;thermal hyperalgesia ENDO+SFN vs ENDO:6.8±1.3 vs 2.7±1.9,p<0.01),ENDO+SFN group,the test on the 21st day showed that mechanical irritation caused hyperalgesia and thermal irritation-induced hyperalgesia were improved compared with ENDO group(mechanical hyperalgesia ENDO+SFN vs ENDO:14.7±2.1 vs 6.4±1.6,p<0.01;thermal hyperalgesia ENDO+SFN vs ENDO 9.7±1.7 vs 4.6±1.4,p<0.01),which lasts until 28 days after surgery.With the continuous injection of the drug,this effect is continuously improved,Compared with ENDO group,there are statistical differences(mechanical hyperalgesia ENDO+SFN vs ENDO:16.2±2.3 vs 6.6±1.4,p<0.01;thermal hyperalgesia ENDO+SFN vs ENDO:11.2±2.0 vs 4.6±.4,p<0.01)..2.Dose effect of sulforaphane in improving hyperalgesia of sciatic nerve endometriosisThe model group was given different concentrations of sulforaphane intervention(5,15,30,60mg/kg).The results showed that compared with the model group,the mechanical hypersensitivity and thermal hyperalgesia decreased by sulforaphane with 15mg/kg,30mg/kg,60mg/kg were administered on the 7,14,21,and 28 days,the thresholds of these groups were significantly improved,with significant differences(all p<0.05);in the range of 15-30mg/kg,the therapeutic effect was dose-dependent with the drug concentration.However,the pain tolerance of the two groups with the drug concentration of 30mg/kg and 50mg/kg had no significant difference(p>0.05).Therefore,the intervention concentration of sulforaphane in the following studies of this project was set at 30mg/kg.3.Sulforaphane inhibits the growth of ectopic endometrial tissue in SNEM animals by down-regulating VEGFIn the model animals of sciatic nerve endometriosis,the volume of endometrial tissue around the sciatic nerve increased,and sulforaphane administration had a therapeutic effect(ENDO+SFN group vs Sham Group:140.2±30 vs 42.6±20 mm3,p<0.01),and the volume decreased by more than 2/3.At the same time,the levels of VEGF protein in the serum and the lesion area of the ENDO group were significantly increased,the serum VEGF protein level in ENDO group was 8 times higher than that in Sham group(ENDO vs Sham:185.3±42.0 vs 23.6±12.8 pg/ml,p<0.001);the level of VEGF protein in the serum of ENDO+SFN group was lower than that of ENDO group(ENDO+SFN vs ENDO:185.3±42.0 vs 69.8±33.0 pg/ml,p<0.01),and recovered to 3 times the level of Sham group,compared with ENDO group Reduced by 2/3.The expression of VEGF protein in the lesion area also showed similar changes.Compared with the Sham group,the ENDO group increased by 5 times(ENDO vs 347.6±67.9 vs Sham:58.9±27.4 pg/ml,p<0.001);the VEGF protein level in the lesion area in the ENDO+SFN group was lower than that in the ENDO group(ENDO+SFN vs ENDO:156.3±49 vs 347.6±67.9 pg/ml,p<0.001),and recovered to 2.5 times the level of the Sham group,compared to ENDO group The group has decreased by more than 50%4.Sulforaphane inhibits inflammation in endometriosis of sciatic nerveIn the superficial layer of spinal cord(L4-6)near sciatic nerve,IL-6 protein expression in the superficial area of the dorsal horn of the spinal cord in the ENDO group was higher than that in the Sham group(ENDO vs Sham:243.7±46.8 vs 74.7±17.9 pg/mg,p<0.01),the expression of IL-6 protein in the ENDO+SFN group was lower than that in the ENDO group(ENDO+SFN vs ENDO:138.3±37 vs 243.7±46.8 pg/mg,p<0.05).The expression of IL-1? protein in the superficial region of the spinal dorsal horn in the ENDO group was higher than that in the Sham group(ENDO vs Sham:154.7±34.1 vs 46.3 ±2.9 pg/mg,p<0.01),the expression of IL-1? protein in the ENDO+SFN group was lower than that in the ENDO group(ENDO+SFN vs ENDO:71.3±21.2 vs 154.7±34.1 pg/mg,p<0.01).The expression of TNF-? protein in the superficial area of the spinal dorsal horn in the ENDO group was higher than that in the Sham group(ENDO vs Sham:197.4±38.3 vs 86.9±19.9 pg/mg,p<0.01),the expression of TNF-? in the ENDO+SFN group was lower than that in the ENDO group(ENDO+SFN vs ENDO:141.1±28.4 vs 197.4±38.3 pg/mg,p<0.05).IL-6,IL-1?,and TNF-? mRNA in ENDO group were significantly higher than those in Sham group,which was consistent with the changes in protein levels detected by ELISA.IL-6 was 3.24 times higher,p<0.001;IL-1? was 2.68 times higher,p<0.01;TNF-?was 3.26 times higher,p<0.001.The expression of inflammatory factors in ENDO+SFN group was lower than that in ENDO group(IL-6 ENDO+SFN vs ENDO group:1.78±0.5 vs 3.24±0.69,p<0.01;IL-1? ENDO+SFN vs ENDO:1.53±0.47 vs 2.68±0.62,p<0.01;TNF-? ENDO+SFN vs ENDO:2.23±0.45 vs 3.26±0.64,p<0.05).5.The COX2 and iNOS expression can be inhibited by sulforaphaneThe mRNA level of COX-2 was significantly increased in ENDO group(3.64 ±0.76),which was 3.6 times higher than that in Sham group(p<0.01),The mRNA expression level of COX-2 in ENDO+SFN group was significantly down regulated(ENDO+SFN vs ENDO:1.97 ±0.44 vs 3.64 ± 0.76,p<0.01)to about 50%of that in ENDO group;the protein level of COX-2 was similar to that in mRNA level,that is,the protein level of COX-2 in ENDO group was more than 3 times higher than that in sham group(3.23±0.63pg/ml),p<0.001;the protein level of COX-2 in ENDO+SFN group was significantly reduced to about half of that in ENDO group(ENDO+SFN vs ENDO:1.79±0.4 vs 3.23±0.63pg/ml,p<0.01).It was found that the mRNA(2.53±0.54)and protein(2.86±0.57 pg/ml)levels of iNOS in ENDO group were 2.5 times higher than those in control group(p<0.01).The mRNA and protein levels of iNOS in ENDO+SFN group were down regulated compared with EDNDO group(mRNA ENDO+SFN vs ENDO:1.84±0.39 vs 2.53±0.54,p<0.05;protein ENDO+SFN vs ENDO 1.98±0.42 vs 2.86±0.57pg/ml,p<0.05),the down-regulation was about 1/3 of the level of ENDO group.6.Keapl/Nrf2 signaling pathway is inhibited in sciatic nerve endometriosis and can be significantly activated by sulforaphaneIn the superficial tissues of the dorsal horn of the spinal cord(L4-6)near the sciatic nerve,it was found that the expression of Keap1 protein was significantly reduced than that in the sham group(ENDO vs Sham:0.32±0.16 vs 1±0.18pg/ml,p<0.01),which was about 30%of the control group.The protein level of Keap1 in ENDO+SFN group was significantly increased than that in ENDO group(ENDO+SFN vs ENDO:0.58±0.19 vs 0.32±0.16pg/ml,p<0.05),which was 1-fold higher than that in ENDO group,reaching 60%of the sham group.The protein level of Nrf2 in ENDO group was significantly lower than that in Sham group(ENDO vs Sham:0.42 ± 0.17 vsl ± 0.2pg/ml,p<0.01),which was about 40%of the level of Sham group.The protein level of Nrf2 in ENDO+SFN group was higher than that in ENDO group(ENDO+SFN vs ENDO:1.67±0.3 vs 0.42±0.17pg/ml,p<0.001),the expression level increased 3 times compared with ENDO group,and reached 1.6 times of Sham group.Conclusions:1.Sulforaphane can treat the pain caused by endometriosis of the sciatic nerve through both anti-inflammatory and analgesic aspects;2.Sulforaphane can inhibit the growth of ectopic endometrial tissue in sciatic nerve endometriosis through VEGF;3.Sulforaphanean can effectively inhibit the expression of IL-6,IL-1?,TNF-?,COX2,iNOS,and relieve the pain of sciatic nerve endometriosis;4.Keap1/Nrf2 signaling pathway is inhibited in sciatic nerve endometriosis,sulforaphane can effectively promote the activation of this signaling pathway. |
PDF Full Text Request