| Objective:Clinical part:Meta-analysis was used to systematically evaluate the clinical efficacy of traditional Chinese medicine in the treatment of diabetic erectile dysfunction(DIED),in order to objectively evaluate the effectiveness and safety of traditional Chinese medicine in the treatment of DIED.In the first part of the experiment,the Sprague Dawley(SD)rat model of Diabetes-induced dysfunction(DIED)was established,and the serum of each group was determined by intervention of high-medium-medium and low-dose groups of Chinese medicine.Sex hormones,blood glucose,sexual function and the expression of related factors in PI3K/Akt and RhoA/Rho signaling pathways in the corpus cavernosum tissues were explored from the perspectives of whole,tissue and molecular levels to explore the mechanism of DIED in the treatment of DIED.Part 2:By establishing a SD rat model of diabetic erectile dysfunction(DIED),the intervention of Shijingtongluo Recipe and its decomposed formulas was performed to determine serum sex hormones,blood glucose,sexual function and corpus cavernosum tissues of each group of rats.The changes of the expression of related factors in PI3K/Akt and RhoA/Rho signaling pathways were discussed at the different levels of the whole,tissues and molecules to explore the compatibility of Filling Tongluo Recipe in the treatment of DIED.Methods:Clinical section:by search including PubMed,Cochrane Library,AMED,EMbase,WorldSciNet,Nature,Science online and China Journal Full-text Database(CNKI),China Biomedical Literature CD-ROM Database(CBM),China Resources Database.Two evaluators independently extracted data and performed methodological quality assessment.Data analysis was performed using RevMan 5.3 software.Part of the experiment:1.90 SD male rats were randomly divided into normal group,DIED model group,positive drug control group,Chinese medicine high-dose group,Chinese medicine middle-dose group,and traditional Chinese medicine low-dose group,with 15 rats in each group.Fifteen of the normal group were not administered,and the remaining five groups of 75 rats were modeled using streptozotocin(STZ).After the model was successful,the normal group was given an equal amount of normal saline.The model group was given a high-fat,high-sugar diet.The positive drug control group was given tadalafil 0.2 mg/kg twice a week.The other groups were given different doses of traditional Chinese medicine for filling Jingjingtong.The above groups of interventions lasted for 4 weeks.After 4 weeks of administration,serum levels of sex hormones were determined by enzyme-linked immunosorbent assay.Western blot and PCR were used to detect nitric oxide synthase(eNOS),threonine protein kinase Akt,RhoA,Expression of Rho kinase and phosphodiesterase type 5(PDE5)-associated protein and mRNA.The changes of serum Ca2+levels in each group were detected by flow cytometry.3 Experimental data were analyzed using SPSS 24.0 statistical software.The second part of the experiment:1.90 SD male rats were randomly divided into normal group,DIED model group,positive drug control group,filling group,Tongluo group and Rongjingtongluo group.Fifteen of the normal group were not administered,and the remaining five groups of 75 rats were modeled using streptozotocin(STZ).After the model was successful,the normal group was given an equal amount of normal saline.The model group was given a high-fat,high-sugar diet.The positive drug control group was given tadalafil 0.2 mg/kg twice a week.The remaining groups were given the corresponding disassembled for treatment.The above groups of interventions lasted for 4 weeks.After 4 weeks of administration,serum levels of sex hormones were determined by enzyme-linked immunosorbent assay.Western blot and PCR were used to detect nitric oxide synthase(eNOS),threonine protein kinase Akt,RhoA,Expression of Rho kinase and phosphodiesterase type 5(PDE5)-associated protein and mRNA.The changes of serum Ca2+levels in each group were detected by flow cytometry.3.Experimental data were analyzed using SPSS 24.0 statistical software.Results:Clinical section:A total of 8 articles,including 585 patients,were included.The use of traditional Chinese medicine alone or in combination with conventional western medicine can significantly improve the IIEF-5 score in DIED patients,and the efficacy of traditional Chinese medicine in improving erectile function in DIED patients is better than that in the control group[95%CI(4.21,5.07),P<0.00001]The total efficacy of traditional Chinese medicine alone or in combination with conventional western medicine for DIED was better than that of the control group[OR=4.83,95%CI(2.81,8.29),P<0.00001].In the experimental part one:1.After 4 weeks of treatment,the sexual function indexes of each group were detected,and the number of snoring,the first crawling time,the number of riding times and the number of insertions were observed.The difference between the model group and the normal group was statistically significant.(p<0.01);There was significant difference between the control group and the high,medium and low dose groups of Chinese medicine and the model group(p<0.05).There was no significant difference between the high dose group and the control group(P>0.05).There was a statistically significant difference between the high-dose group and the low-dose group(p<0.05).2.The results of blood glucose index test showed that the difference between the model group,the control group and the high,middle and low dose groups of traditional Chinese medicine was significantly higher than that of the normal group(p<0.01).After treatment,the control group and Chinese medicine were high.There was no significant difference between the middle and low dose groups and the model group(p>0.05).3.Serum sex hormone levels showed that Jingjing Tongluo Chinese medicine can significantly increase serum T levels in rats.The serum T of the model group was significantly lower than that of the normal group(P<0.01);the serum T of the high,medium and low dose groups of Chinese medicine was significantly higher than that of the model group(P<0.05);the serum T of the high dose group of Chinese medicine was significantly higher than the traditional Chinese medicine.Low dose group(P<0.05).The histopathological examination of the corpus cavernosum of each group showed that the capillaries of the corpus cavernosum of the normal group were rich in mucosal intertwined,and the vascular endothelial cells of the corpus cavernosum in the model group were lower than those in the normal group,suggesting that the blood vessels were destroyed and the number of red blood cells decreased.,a large number of connective tissue hyperplasia can be seen.The number of red blood cells in the corpus cavernosum vessels of the other groups increased compared with the DIED group,and the connective tissue was not significantly different.Real-time quantitative PCR showed that compared with the normal group,the mRNA levels of eNOS and Aktl in the model group decreased significantly(P<0.01,P<0.05).Compared with the model group,the control group,Chinese medicine high,medium,The mRNA levels of eNOS and Aktl in the low-dose group increased significantly(P<0.05).Compared with the control group,the mRNA levels of eNOS and Aktl in the high-dose group did not change significantly(P>0.05).Compared with the normal group,the mRNA levels of RhoA,ROCK1,ROCK2 and PDE5A in the corpus cavernosum of the model group were significantly increased(P<0.05,P<0.01,P<0.01,P<0.01);Compared with the control group,the mRNA levels of RhoA,ROCK1,ROCK2 and PDE5A in the high,medium and low dose groups of Chinese medicine were significantly lower(P<0.05).Compared with the control group,the RhoA,ROCK1,ROCK2 and PDE5A in the high dose group of traditional Chinese medicine were compared.There was no significant change in mRNA level(P>0.05).Compared with the low-dose group,the mRNA levels of RhoA,ROCK1,ROCK2 and PDE5 in the high-dose group were significantly lower(P<0.05).Western blot results showed that the protein expression levels of eNOS and Aktl in the model group were significantly lower than those in the normal group(P<0.01).Compared with the model group,the protein expressions of eNOS and Aktl in the control group and the Chinese medicine group were significantly higher.Increased increase(P<0.05).Compared with the normal group,the RhoA,ROCK1,ROCK2 and PDE5 protein levels in the model group were significantly increased(P<0.01,P<0.01,P<0.05,P<0.01).Compared with the model group,the control group and the Chinese medicine were higher.The expressions of RhoA,ROCK1,ROCK2 and PDE5 in the middle and low dose groups were significantly decreased(P<0.05)Compared with the control group,the expression levels of RhoA,ROCK1,ROCK2 and PDE5 in the high dose group had no significant changes.P>0.05);Compared with the low dose group of traditional Chinese medicine,the expression of RhoA,ROCK1,ROCK2 and PDE5 protein in the high dose group of Chinese medicine was significantly lower(P<0.05).The serum Ca2+level by flow cytometry showed that the serum Ca2+level in the model group was significantly higher than that in the normal group(P<0.01).Compared with the model group,the serum Ca2+level in the Chinese medicine group was significantly lower(P<0.05).Compared with the low-dose group of traditional Chinese medicine,the serum Ca2+level in the high-dose group of Chinese medicine was significantly lower(P<0.05).Experimental part 2:1.After 4 weeks of treatment,the sexual function indexes of each group were detected,and the number of snoring,the time of first crawling,the number of riding times and the number of insertions were observed.The difference between the model group and the normal group was statistically significant.(p<0.01);There was significant difference between the control group,the refining group,the Tongluo group,the refining and meridian group and the model group(p<0.05).There was no significant difference between the refining and meridian group and the control group(P>0.05);There was significant difference between the filling and refining group and the refining group and Tongluo group(p<0.05).There was no significant difference between the refining group and the Tongluo group(P>0.05).2.The results of blood glucose index test showed that the differences between the model group,the control group,the Chinese medicine group and the normal group were highly statistically significant(p<0.01).There was no statistical difference between the control group and the Chinese medicine group and the model group after treatment.Academic significance(p>0.05).3.Serum sex hormone levels showed that Jingjing Tongluo can significantly increase serum T levels in rats.The serum T of the model group was significantly lower than that of the normal group(P<0.01).The serum T of the filling group was significantly higher than that of the filling group and the Tongluo group(P<0.05).The histopathological examination of the corpus cavernosum of each group showed that the capillaries of the corpus cavernosum of the normal group were rich in mucosal intertwined,and the vascular endothelial cells of the corpus cavernosum in the model group were lower than those in the normal group,suggesting that the blood vessels were destroyed and the number of red blood cells decreased.,a large number of connective tissue hyperplasia can be seen.The number of red blood cells in the corpus cavernosum vessels of the other groups increased compared with the DIED group,and the connective tissue was not significantly different.Real-time quantitative PCR showed that the mRNA levels of eNOS and Aktl in the model group were significantly lower than those in the normal group(P<0.01,P<0.05).Compared with the model group,the control group,the refining group,and the control group.The mRNA levels of eNOS and Aktl in the group and the filling group were significantly increased(P<0.05)Compared with the control group,the mRNA levels of eNOS and Aktl in the Gujingtongluo group did not change significantly(P>0.05).Compared with the normal group,the mRNA levels of RhoA,ROCK1,ROCK2 and PDE5A in the corpus cavernosum of the model group were significantly increased(P<0.05,P<0.01,P<0.01,P<0.01);Compared with the group,the mRNA levels of RhoA,ROCK1,ROCK2 and PDE5 in the Jiejingtongluo group were significantly lower(P<0.05).Western Blot results showed that the protein expression levels of eNOS and Aktl in the model group were significantly lower than those in the normal group(P<0.01).Compared with the model group,the control group and the filling group,Tongluo group,and Jingjingtongluo The protein expression of eNOS and Aktl in the group increased significantly(P<0.05).Compared with the normal group,the RhoA,ROCK1,ROCK2 and PDE5 protein levels in the model group were significantly increased(P<0.01,P<0.01,P<0.05,P<0.01);compared with the model group,the control group and the refining group The expression levels of RhoA,ROCK 1,ROCK2 and PDE5 in the Tongluo group and the Rongjingtongluo group were significantly decreased(P<0.05).Compared with the filling group,the RhoA,ROCK1,ROCK2 and PDE5 protein levels in the Jiejingtongluo group were compared.The expression was significantly reduced(P<0.05).The results of flow cytometry detection of serum Ca2+ showed that the serum Ca2+ level in the model group was significantly higher than that in the normal group(P<0.01).Compared with the model group,the serum of the filling group,Tongluo group and Rongjingtongluo group The Ca2+level was significantly lower(P<0.05).Compared with the filling group,the serum Ca2+level in the Jiejingtongluo group was significantly lower(P<0.05).Conclusion:Clinical part:Chinese medicine alone or in combination with conventional western medicine can better improve the erectile function of DIED patients.Among them,in the process of DIED treatment,traditional Chinese medicine is one of the most frequently used traditional Chinese medicines for filling and refining Tongluo,tonifying kidney and filling essence,and activating blood circulation and collaterals as the basic treatment rule has been widely used in the clinical practice of DIED,and no serious adverse reactions have been reported.An effective and safe method for treating DIED has high application value and promotion significance.Experimental part 1:1.Filling Jingjingtong traditional Chinese medicine can improve the erectile function of DIED rats,and the effect of filling high dose group of traditional Chinese medicine is more significant.2.The possible mechanism of filling Jingjingtongzhong Chinese medicine to improve erectile dysfunction in DIED rats is to up-regulate the expression of Aktl in PI3K/Akt signaling pathway and down-regulate the expression of RhoA,ROCK1 and ROCK2 proteins in RhoA/Rho pathway,leading to eNOS phosphorylation.It can reduce the Ca2+level and the expression of PDE-5 protein,promote the relaxation of cavernous smooth muscle and reduce the contraction of cavernous smooth muscle,and achieve the purpose of treating diabetic ED.3.Key molecules targeting PI3K/Akt and RhoA/Rho signaling pathways can provide an important basis for PI3K/Akt and RhoA/Rho to become new targets for DIED treatment,and provide an alternative new method for DIED treatment.Experimental part 2:1.Filling the traditional Chinese medicine and its decomposed formula can improve the erectile function of DIED rats.The role of the filling and meridian group in the sexual function and serum sex hormones of rats is better than that of the simple filling group or pass.The group,Chinese medicine treatment of diabetic erectile dysfunction,should adhere to the principle of comprehensive treatment of filling and clearing the network.2.The possible mechanism of filling Jingjingtongzhong Chinese medicine to improve erectile dysfunction in DIED rats is to up-regulate the expression of Aktl in PI3K/Akt signaling pathway and down-regulate the expression of RhoA,ROCK1 and ROCK2 proteins in RhoA/Rho pathway,leading to eNOS phosphorylation.It can reduce the Ca2+level and the expression of PDE-5 protein,promote the relaxation of cavernous smooth muscle and reduce the contraction of cavernous smooth muscle,and achieve the purpose of treating diabetic ED.3.Filling the essence and compatibility of the whole party is superior to other combinations,reflecting the overall concept of TCM treatment.Filling the essence of traditional Chinese medicine will have different sexual tastes,and the drugs with different effects will be combined with each other to reflect the synergistic effect of the compatibility of the prescriptions,thus forming the best compatibility form,confirming... |
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