| Objective:In the clinical trial part of this study,Yunfu Tongjing massage was used to treat painful diabetic peripheral neuropathy(PDPN).To evaluate the changes of TCM syndrome score,nerve conduction velocity and glucose metabolism in patients with Yunfu Tongjing massage,and to analyze its clinical efficacy.In the animal experiment part,Yunfu Tongjing Tuina was used to intervene in rats with painful diabetic peripheral neuropathy.The effect of Yunfu Tongjing Tuina on JAK2 / STAT3 signaling pathway in model rats was analyzed,and the possible mechanism of Yunfu Tongjing Tuina in the treatment of painful diabetic peripheral neuropathy was explored,which provided a basis for its promotion and application.Methods:(1)Clinical study on the improvement of PDPN by abdominal meridian massage.Seventy-two patients diagnosed with painful diabetic peripheral neuropathy were randomly divided into massage group and control group according to the random number table method.Both groups maintained the original hypoglycemic regimen and the original treatment of other diseases.The control group was treated with oral mecobalamin tablets 0.5mg,3 times/day.The massage group was treated with Yunfu Tongjing massage on the basis of the control group,5 days as a course of treatment,with a two-day break between courses,a total of 4 courses of treatment.After the intervention,the blood biochemical indexes,TCM clinical symptom scores(total score,main symptom score),nerve conduction velocity,visual analogue score(VAS),Toronto clinical system score(TCSS)and adverse reactions during the treatment were observed before and after treatment.SPSS software was used for data statistical analysis to evaluate the clinical efficacy of Yunfu Tongjing massage in the treatment of PDPN with yang deficiency and cold coagulation syndrome.(2)Experimental study on improving glucose and lipid metabolism in PDPN rats by Yunfu Tongjing Tuina method.26 rats were randomly divided into blank group,model group and massage group.The blank group was fed routinely without any treatment.The model group and the massage group were induced by streptozotocin(STZ)to induce PDPN rat model.By measuring the pain threshold of the rats,the PDPN model rats were screened out.The PDPN model rats were divided into massage group and model group.The massage group was treated with massage once a day,5 times as a course of treatment,2 days of rest between courses,a total of 4 courses of treatment.After giving relevant intervention treatment,the general state and weight of rats in each group were observed,and the changes of FBG,GSP,CHO,TG,LDL-C and HDL-C were detected to explore the effect of abdominal massage on glucose and lipid metabolism in PDPN rats.(3)Effect of Yunfu Tongjing Tuina on pain behavior and nerve conduction velocity in PDPN rats.The changes of thermal sensitivity threshold(TWL)and tail flick test were observed at 0 week before intervention and 2 weeks and 4 weeks after intervention.The changes of sciatic nerve conduction velocity in each group were detected at 4 weeks,and the effects of abdominal meridian massage on pain behavior and nerve conduction velocity in PDPN rats were explored.(4)The effect of Yunfu Tongjing Tuina on the morphology of sciatic nerve in PDPN rats.After the intervention,the experimental rats were taken,and the sciatic nerve of the rats was stained with hematoxylin-eosin staining(HE staining),solid blue staining(LFBstaining),and glycine silver staining(silver plating)to observe the pathological changes of the sciatic nerve of the rats.The ultrastructure of sciatic nerve in rats was observed to explore the effect of Yunfu Tongjing massage on the morphology of sciatic nerve in PDPN rats.(5)The effect of Tuina on JAK2/STAT3 signaling pathway in spinal cord of PDPN rats.After the intervention,the rats were deeply anesthetized and the expression of SOCS1,IL-6,IL-10 and IL-18 in serum was detected by ELISA.The expression of JAK2,STAT3,pJAK2 and p-STAT3 m RNA in spinal cord tissue of rats was detected by RT-q PCR.WesternBlot method was used to detect the expression of JAK2,STAT3,p-JAK2 and p-STAT3 in spinal cord tissue of rats.Finally,SPSS software was used to analyze all the results to explore the effect of Yunfu Tongjing Tuina on JAK2/STAT3 signaling pathway in spinal cord of PDPN rats.Results:(1)The results of glucose and lipid metabolism showed that FBG,2h PG and Hb A1 C in the massage group were lower than those before treatment(P<0.05).After treatment,TG,TC,LDL-C and HDL-C in the massage group were improved compared with those before treatment(P<0.05).The comparison between the two groups showed that the improvement of TG and TC in the massage group was better than that in the control group(P<0.05).The results of statistical analysis of TCM scale showed that the scores of TCM syndrome scale before and after treatment in the massage group were statistically significant(P<0.001),and the scores in the massage group were better than those in the control group(P<0.05).The results of clinical efficiency showed that the total effective rate of the control group was72.22 %,and the total effective rate of the massage group was 88.89 %.The difference was statistically significant(P<0.05).The results of nerve conduction velocity showed that after treatment,the massage group was superior to the control group in improving the MNCV of the right median nerve,the SNCV of the left and right sural nerves,and the MNCV of the left and right common peroneal nerves(P<0.05).The results of TCSS score and VAS score showed that the TCSS score and VAS score of the two groups were lower than those before treatment,and the score of the massage group was better than that of the control group(P<0.05).(2)Before intervention,compared with the blank group,the FBG of the model group and the massage group was significantly increased(P<0.001),and there was no difference between the model group and the massage group.After 4 weeks of intervention,compared with the model group,the FBG content of the rats in the massage group decreased(P<0.001);the GSP level of the PDPN model group was higher than that of the blank group(P<0.05),and the GSP level of the massage group was lower than that of the model group(P<0.05).Before intervention,compared with the blank group,the levels of CHO,TG and LDL-C in the model group and the massage group were increased(P<0.001),and the level of HDL-C was decreased(P<0.001).After 4 weeks of intervention,compared with the model group,the levels of CHO,TG and LDL-C in the massage group decreased,and the level of HDL-C increased,the difference was statistically significant(P<0.05).(3)The results of thermal threshold determination showed that compared with the blank group,the TWL of the model group and the massage group decreased,with statistical significance(P<0.001,P<0.001).After 4 weeks of intervention,the TWL of the massage group was higher than that of the model group,with statistical significance(P=0.001);the results of the tail-flick test showed that before the intervention,compared with the blank control group,the tail-flick latency of the model group and the massage group increased,with statistical significance(P<0.001,P<0.001).After 4 weeks of intervention,compared with the PDPN model group,the tail-flick latency of the massage group was decreased,which was statistically significant(P=0.008).The results of nerve conduction velocity showed that compared with the blank group,MNCV and SNCV in the model group decreased,with statistical significance(P<0.05).MNCV and SNCV in the massage group were higher than those in the model group,with statistical significance(P<0.05).(4)The results of HE staining,LFB staining and silver staining showed that the demyelination of sciatic nerve in the massage group was alleviated,and the axons of a few nerve fibers were swollen,vacuolated and degenerated,which were lighter than those in the model group and heavier than those in the blank group.The results of ultrastructural observation of sciatic nerve showed that the Schwann cells of sciatic nerve in the model group were moderately edematous,the nucleus was irregular,chromatin was condensed,mitochondria were moderately swollen,the matrix in the membrane became pale,and the ridge decreased and disappeared.In the Tuina group,the cell membrane of the sciatic nerve Schwann cells in the rats was partially damaged and dissolved,the membrane structure was partially blurred,the mitochondria were slightly swollen,and a small amount of ridges were broken.Demyelination changes and myelin rupture were observed in the local area.(5)Compared with the blank group,the levels of serum SOCS-1 and IL-10 in the model group decreased,and the levels of IL-6 and IL-18 increased,all of which were statistically significant(P < 0.05).Compared with the model group,the levels of serum SOCS-1 and IL-10 in the massage group increased,the difference was statistically significant(P < 0.05),and the levels of IL-6 and IL-18 decreased,with statistical significance(P < 0.05).The results of RT-q PCR showed that compared with the model group,JAK2 m RNA and STAT3 m RNA in the massage group decreased,with statistical significance(P<0.05).The results of Western-Blot showed that compared with the model group,the expression of JAK2 and STAT3 protein in the massage group decreased,with statistical significance(P < 0.05),and the expression of p-JAK2 protein decreased,with statistical significance(P<0.05).Conclusion:(1)The clinical efficacy of western medicine combined with Yunfu Tongjing Tuina in the treatment of PDPN(Yang deficiency and cold coagulation type)is better than that of western medicine alone.It is suggested that Yunfu Tongjing Tuina can improve the symptom score and nerve conduction velocity of patients,and has a certain effect on improving the disorder of glucose and lipid metabolism.It is safe and has no obvious side effects and adverse reactions.(2)Yunfu Tongjing Tuina can effectively improve the general conditions of PDPN rats,such as mental retardation,polydipsia,polyphagia,polyuria,emaciation,and dry hair color,and can improve the glucose and lipid metabolism disorders of PDPN rats.(3)Yunfu Tongjing Tuina method can effectively improve the thermal threshold and pain behavior of PDPN rats,and improve the nerve conduction velocity of PDPN rats.(4)Yunfu Tongjing Tuina method can improve the changes of neuropathological structure and ultrastructure of PDPN rats,reduce the damage of sciatic nerve axons and myelin sheaths,and protect the nerves of rats.(5)Yunfu Tongjing Tuina can protect the nerves of rats.Part of the mechanism may be related to inhibiting the phosphorylation of JAK2 and STAT3,inhibiting the overexpression of JAK2/STAT3 signaling pathway and reducing the inflammatory response. |
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