| BackgroundLow back pain(LBP)is a chronic and global health problem.More than 80 percent of people will undergo low back pain in their lifetime.Lumbar disc herniation(LDH)and lumbar disc degenerative disease(IDD)are the main causes of LBP.There is a close causal relationship between IDD and LDH.The further development of IDD can gradually evolve into LDH.Most patients with LDH can be improved or clinically cured with nonsurgical treatment.For thousands of years,TCM has played an important role in non-surgical treatment.Through the follow-up with more than 500 cases,our research group confirmed the effectiveness of the conservative treatment of LDH with Yiqi Huoxue Recipe,and found the "Resorption" phenomenon of ruptured lumbar disc herniation through MRI examination.Moreover,our basic studies confirmed that autophagy was closely related to LDH previously,and the existence of autophagosome was observed by electron microscopy.MethodsThe first part:from January 2000 to January 2020,CNKI,VIP,Wan Fang data and other databases were searched for meta-analysis of the clinical literatures on the treatment of LDH with Chinese herbal compound.The total effective rate,publication bias,VAS score,JOA score,ODI score and laboratory examination index were evaluated.At the same time,the frequency and classification frequency of traditional Chinese medicine were counted and compared with the group of Yiqi Huoxue Recipe.The second part:From February 2011 to February 2014,75 patients with single level RLDH in the outpatient department of Suzhou Hospital of TCM were selected.They were treated with Yiqi Huoxue Recipe and followed up for 5 years.JOA score,straight leg elevation angle and finger to ground distance were measured on the basis of before treatment,3 months,6 months,1 year,2 years and 5 years after treatment;JOA improvement rate and protrusion volume resorption rate were calculated at the last follow-up.The third part:The rat models of ruptured disc herniation(experiment 1 and experiment 2)and intervertebral disc degeneration were established.We studied the effect of Yiqi Huoxue Recipe on RLDH and IDD in rats by regulating autophagy.In Experiment 1,Experimental study on the effect of Yiqi Huoxue Recipe regulating autophagy on ruptured intervertebral disc herniation in rats.In Experiment 2,Mechanism of Yiqi Huoxue Recipe legulating autophagy and promoting resorption of ruptured intervertebral disc herniation in rats.In Experiment 3,Experimental study on the effect of Yiqi Huoxue Recipe on the degeneration of intervertebral disc in rats by regulating autophagy.In Experiment 4,Mechanism of Yiqi Huoxue Recipe regulating autophagy and inhibiting intervertebral disc degeneration in rats.The mechanism of Yiqi Huoxue Recipe regulating autophagy and its effect on different degrees of intervertebral disc herniation were evaluated by MRI,ELISA,immunohistochemistry,Western blot and qPCR.ResultsThe first part:Finally,23 articles were included,including 2675 patients with LDH,1385 patients in the treatment group and 1290 patients in the control group.(1)Total effective rate:the effective rate of the treatment group was significantly higher than that of the control group,Z=10.70,P<0.00001.(2)VAS score:The improvement of pain in the treatment group was significantly better than that in the control group,Z=9.60,P<0.00001.(3)JOA score:The symptoms of low back pain in the treatment group were significantly improved,Z=3.72,P=0.0002.(4)ODI score:The improvement degree of the treatment group was better than that of the control group(P<0.00001).(5)A total of 84 Chinese herbal medicines were included,with a total frequency of 272 times.(6)Compared with Yiqi Huoxue prescription,9 kinds of Traditional Chinese Medicine accounted for 18.01%of the total frequency of Traditional Chinese Medicine.The second part:A total of 71 patients with RLDH were followed up.(1)Clinical results(JOA score,straight leg elevation angle and finger to ground distance):compared with conditions before treatment,there were significant improvements at 3 months,6 months,1 year,2 years and 5 years after treatment(P<0.001).(2)Imaging results:the volume of protrusion decreased from 1981.73±588.72 mm3 to 1011.82±395.47 mm3 in the first and last follow-up of 71 patients with RLDH(t=13.151,P<0.001).At the last follow-up,the resorption of protrusions was as follows:there were 24 cases with obvious absorption,26 cases with partial absorption,19 cases without absorption and 2 cases with enlargement.The RR was 45.65±2.83%.The third part:Experiment 1:After 4 weeks of treatment,the intervertebral disc resorption of RLDH rats in Yiqi Huoxue Recipe group was significantly increased;Western blot and qPCR results showed that the expression levels of AMPK,LC3,VPS34,Beclinl and USP13 in Yiqi Huoxue Recipe group were significantly increased(P<0.01);The results of immunofluorescence showed that the expression of USP13 was significantly increased after Yiqi Huoxue Decoction treatment.(P<0.01).The results of immunoprecipitation showed that Yiqi Huoxue Decoction could induce the formation of VPS34/Beclin1 complex(P<0.01).Experiment 2:3-MA partly inhibited the reabsorption promoting effect of Yiqi Huoxue Formula after treatment(P<0.05 or P<0.01);3-MA inhibited the expression of AMPK,VPS34 and LC3 induced by Yiqi Huoxue Recipe(P<0.01);the experimental results of Spautin-1 autophagy inhibition were consistent with 3-mA.Experiment 3:the levels of IL-1β was obviously decreased after treatment with Yiqi Huoxue Recipe(P<0.01);In the Yiqi Huoxue Decoction group,the MRI signal of caudal intervertebral disc was significantly increased and Pfirrmann score was significantly decreased(P<0.05 or P<0.01);Western blot and qPCR results showed that the expression levels of AMPK,VPS34,PI3K,USP13 and Beclin1 in Yiqi Huoxue Decoction group were significantly increased(P<0.05 or P<0.01);The results of immunoprecipitation showed that Yiqi Huoxue Decoction could induce the formation of VPS34/Beclinl complex(P<0.01).Experiment 4:3-MA inhibited the protein expression of LC3,VPS34 and Beclin1 induced by Yiqi Huoxue Recipe;immunoprecipitation also showed that 3-MA inhibited the formation of VPS34/Beclin1 complex.The results of spautin-1 autophagy inhibition were consistent with that of 3-MA.ConclusionThe first part:(1)Traditional Chinese medicine compound is effective in treating LDH.(2)The composition of Yiqi Huoxue recipe is universal,scientific and representative.The second part:(1)It is effective in the treatment of RLDH and it can cause resorption under the intervention of Yiqi Huoxue Recipe.(2)This study provides important guidance for the future clinical treatment of RLDH.The third part:(1)Yiqi Huoxue recipe can activate AMPK signaling pathway,induce USP13 formation,inhibit Beclinl ubiquitination,promote the formation of VPS34/Beclinl complex,and stimulate autophagy of intervertebral disc.It can protect degenerative intervertebral disc and promote the degradation of ruptured and herniated intervertebral disc.(2)In the early stage of disc herniation(IDD),we can intervene in advance according to the concept of prevention before illness.For RLDH patients with severe clinical symptoms and obvious MRI images,we can also promote the resorption of prominent tissues and treat the disease through the intervention of Yiqi and Huoxue recipe. |
PDF Full Text Request