| Background:Lumbar disc herniation(LDH)is a common disease in clinical orthopedics,with low back pain and even leg pain as the main symptoms,and in which a painful and numbing symptoms in the leg is caused by compression of the sciatic nerve by the herniated disc.The treatment of this disease is mainly conservative,and Western medicine can relieve symptoms obviously by symptomatic treatment such as anti-inflammatory pain,dehydration and swelling,and nutritional nerve.But it is easy to be repeated,and long-term medication will negatively affect the body.Severe LDH have no choice but to surgical management.Traditional Chinese medicine(TCM)is the preferred method for the treatment of LDH,because it has many advantages,such as obvious efficacy,price relatives,no obvious toxic and side effects.As a common meridian prescription,SANBI decoction can be used to treat a class of diseases caused by resistance to wind cold and wet dampness and is widely used in orthopedic diseases,but its specific clinical efficacy and analgesic mechanism for treating LDH with sciatica remain unclear.Therefore,this study firstly through clinical observation to clarify the clinical efficacy of SANBI Decoction in the treatment of LDH(cold dampness Bi blocked type),so as to provide a new approach for integrated traditional Chinese and Western medicine to treat this disease.Next,network pharmacology was used to explore the possible molecular mechanism of SANBI Decoction in the treatment of LDH and sciatica.At last,we clarified the analgesic mechanism of SANBI Decoction water decoction by making CCI model(chronic nerve compression model).Through clinical observations and basic experiments,we can clarify the efficacy and mechanism of SANBI decoction,which may provide a reference for clinical treatment of LDH as well as the pain it causes.Part Ⅰ:Clinical observationsObjective:To explore the efficacy and safety of SANBI Decoction for treating cold dampness blocked LDH with sciatica through clinical observation.Methods:In this study,a total of 90 patients with LDH were enrolled by strict nanoexclusion criteria,and the patients were randomly divided into three groups according to a random number table,consisting of a simple control group,a Chinese medicine group,and a treatment group with 30 patients in each group.The control group was treated with western medicine alone(mainly pain relief plus nutritional nerves),while the Chinese medicine group was treated with oral administration of SANBI decoction.The treatment group was based on the control group with the addition of SANBI decoction.The treatment duration of all three groups was 4 weeks.The changes of VAS scores and ODI scores before and after treatment in the three groups were observed nodes were treated for 2 weeks,4 weeks and 4 weeks off treatment,efficacy was evaluated by macnab evaluation criteria and adverse effects were recorded during treatment.Results:The general data of the patients in the three groups were not statistically different from each other and were comparable at baseline(P>0.05).Before treatment,there were no significant differences among groups in all scores,and baseline was comparable between the three groups(P>0.05).After 2 weeks of medication,the VAS scores and ODI scores of each of the three groups were reduced compared with before,and the comparisons were statistically different(P<0.05).Two weeks after medication,the excellent rate was 66.67%in the control group,73.08%in the Chinese medicine group,and 78.57%in the treatment group.After four weeks of medication,the scores on each scale were further reduced and the differences were statistically significant(P>0.05)compared with those at two weeks of medication.After 4 weeks of medication,there was no statistically significant difference between groups in lumbar VAS score and ODI score(P>0.05),while there was statistically significant difference in leg VAS score,treated group compared to the control group alone(P<0.05).The excellent rate reached 81.48%in the control group,84.62%in the Chinese medicine group and 92.86%in the treatment group at 4 weeks of medication,which was not statistically different(P>0.05).In terms of lumbar VAS scores after 4 weeks off medication compared with 4 weeks on medication,the treated group had statistically significant differences(P<0.05)from the control group alone.In terms of leg VAS scores,there were statistically significant differences between the treatment groups compared with the vehicle only group(P<0.05)and the TCM group compared with the vehicle only group(P<0.05).In terms of ODI scores,statistically significant differences(P<0.05)were observed between the treatment groups compared with the control group alone.In terms of efficacy evaluation,the excellent rate was 66.67%in the control group,88.46%in the Chinese medicine group,and 92.86%in the treatment group,compared among the three groups,and the difference was statistically significant(P=0.024).No serious adverse reactions occurred in the three groups,and only one patient with post medication diarrhea occurred in the Chinese medicine group and the treatment group,all of whom recovered after self adjustment.Conclusions:SANBI decoction can effectively reduce low back and leg pain and improve lumbar function in patients with LDH with sciatica,and the clinical efficacy is exact,and the treatment process is safe and reliable.Not only that,SANBI decoction is more superior in relieving leg pain,and the efficacy is long-lasting.Our formula can still maintain a high efficacy after 4 weeks withdrawal,which is worth clinical promotion and popularity.Part Ⅱ:Network pharmacology researchObjective:To investigate the pharmacological mechanism of SANBI Decoction on LDH and sciatica.Methods:Active ingredients and medicinal targets of SANBI Decoction were screened out through TCMSP database,and subsequently,the obtained names of target proteins were converted into gene symbol based on UniProt library.The targets of LDH were retrieved from genecards and OMIM databases and further screened.Drug disease co targets were derived by Excel screening and Venn diagram was performed.Using cytoscape3.7.0 software,drug and disease active ingredient target network maps were constructed.The protein interaction network of the targets of action was constructed using string database and analyzed accordingly with R3.6.3 software.The "" clusterprofiler"" R package was used to perform go analysis and KEGG analysis of the significant targets screened by the drugs,and the results were processed and analyzed by R software.Results:the screening resulted in 291 active ingredients and 194 drug disease targets.The commonly used TCM ingredients were beta sitosterol,sitosterol,kaempferol,mairin,quercetin;the key targets were PTGS2,ncoa2,ptgs1,ESR1 through the drug disease ingredient target network diagram.The consensus target PPI network obtained nodes with degree value≥36,which were 5 potential targets of STAT3,mapkl,Jun,mapk3 and AKT1.Go analysis resulted in a total of 2821 enriched entries,including 2522 in biological process,126 in molecular function and 173 in cellular composition(P<0.05).The 171 pathways including IL-17 signaling pathway,TNF pathway were enriched by KEGG analysis(P<0.05).Conclusion:There are many ingredients and abundant targets in SANBI decoction,which can exert anti-inflammatory,immune response,apoptosis,metabolism,antitumor,antiviral,and anti arteriosclerosis effects through many pathways,thus achieving the goal of treating LDH and sciatica.Part Ⅲ:Basic Experimental ResearchObjective:To investigate the mechanism by which aqueous extract of SANBI Decoction alleviates chronic neuropathic pain.Methods:The mice were randomly divided into five groups with six mice in each group,which were divided into control group,module building group,low SANBI Decoction group,high SANBI Decoction group and gabapentin group,respectively.The control group was not modeled,and the other groups were subjected to the fabrication of CCI model,and the mice were intragastrically administered on the first postoperative day,while the low-dose group and high-dose group were given different doses of a water extract of SANBI decoction,the model group was given normal distilled water,and the gabapentin group was given gabapentin water solubilizer.MWT and TWL measurements on the modeling side of the mice were performed at 2 h postdose on days 1,3,5,7,9,11,and 13 after surgery.For small animal ethology,mice were killed by decapitation at the end of the experiment and 14-16 DRG(dorsal root ganglia)from the modeling side were collected to examine TRPV1 expression in tissues and cells by Q-PCR,Western blotting,and Ca2+imaging.Results:Animal behavioral experiments showed that aqueous extract of SANBI Decoction significantly reduced the irritant responses to mechanical pain and thermal pain in CCI model mice.Q-PCR and Western blotting indicated that SANBI Decoction decreased TRPV1 mRNA expression in DRGs of CCI model mice.The results obtained by Ca2+ imaging technique indicated that SANBI decoction could affect TRPV1 activity in DRG neurons of CCI mice.Conclusions:SANBI decoction may alleviate neuropathic pain by reducing TRPV1 expression and activity. |
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