| Purpose: By observing the clinical effect of Qigui Tangtongning Granules on patients with DPN and the effect on the expressions of PERK and CHOP in diabetic model rats,the intervention mechanism of Qigui Tangtongning Granules on DPN based on the PERK signaling pathway was investigated.Method: 1 Clinical study A total of sixty DPN patients diagnosed as deficiency of Qi and Yin combined with stasis were randomly divided into control group and treatment group(thirty in each group).Patients in the two groups were given diabetes education,diet and exercise control,hypoglycemic treatment and oral metocobalamin tablets as the basic treatment.The treatment group was added to the basic treatment with Qigui Tangtongning Granules.The observation period was 12 weeks.The changes of blood glucose,blood lipid and glycosylated hemoglobin in the two groups before and after treatment were recorded and compared.And the changes of TCM symptom score,TCSS score,nerve conduction velocity and serum AGEs before and after intervention in the two groups were compared and analyzed to calculate the total effective rate and determine the intervention effect.2 Animal experiment Ten of 70 male SD rats were randomly selected as the blank control group,and the remaining 60 rats were treated with high-fat diet and STZ intraperitoneal injection(35mg/kg)to induce DM in rats.After successful modeling,the rats were randomly divided into model group,western medicine group and low,medium and high dose groups.Rats in the blank group and the model group were given normal saline gavage,and those in the western medicine group were given mecobalamin gavage.And the high,medium and low dose groups were gavaged with Qigui Tangtongning Granules at a ratio of 2:1:0.5.The experiment lasted for 12 weeks,during which the general conditions of each group of rats were observed.Mechanical pain threshold and sciatic nerve conduction velocity were recorded and compared.Abdominal aortic blood and the sciatic nerve tissues of each group were collected to detect the serum AGEs level of the rats.The expressions of PERK and CHOP in rat sciatic nerve were detected by Western blot.The number of rat sciatic nerve cell apoptosis was detected by TUNEL staining.Results: 1 Clinical findings Clinical study results showed that the total effective rate of the treatment group was 82.76% after 12 weeks of intervention,which was higher than the total effective rate of the control group(62.06%)(P<0.01).After treatment,the TCM syndrome score and TCSS score of the two groups were improved compared with those before treatment,the difference was statistically significant(P<0.01),and the improvement in the treatment group was better than that in the control group(P<0.01 or P<0.05).After intervention,FPG,2h PG and Hb A1 c levels in the treatment group were significantly lower than before treatment(P<0.01),and the decrease was more significant in the treatment group(P<0.05).Compared with before treatment,TG,TC and LDL-C levels in the two groups decreased(P<0.05 or P<0.01)and HDL-C levels increased(P< 0.01).The treatment group was better than the control group in improving TC and HDL-C(P<0.05).After intervention,the median nerve MCV in the treatment group and the median nerve SCV,peroneal nerve MCV and sural nerve SCV in the two groups were all improved(P<0.05 or P<0.01).The nerve conduction velocity was all improved compared with that before treatment(P<0.01).The improvement of median nerve SCV and sural nerve SCV in the treatment group was more significant(P<0.05).The serum AGEs level of the treatment group and the control group was significantly improved compared with that before the intervention(P<0.01),and the treatment group was significantly better than the control group(P<0.01).2 Animal experiment results Animal experimental results showed that,after 12 weeks of intervention,compared with rats in the blank group,rats in the model group and the treatment group all lost weight(P<0.05),and rats in the medium dose group gained weight compared with the model group(P<0.05).Compared with the blank group,FPG increased significantly in the model group(P<0.01),and decreased in the medium and high dose groups compared with the model group(P<0.05).Rats compared with the blank group,model group rats serum AGEs level rise,PWMT and MCV reduced(P<0.05).Compared with model group rats,serum AGEs of rats in each group of TCM intervention decreased(P<0.05),PWMT increased(P<0.05),and MCV of rats in the middle and high dose groups increased significantly(P<0.05).The improvement of the above indexes in the high dose group was significantly better than that in the low dose group(P<0.05).In terms of improving the pathomorphology of sciatic nerve,the nerve damage in the treatment group was alleviated to a certain extent compared with that in the model group.Western blot results showed that compared with the blank group,the expression levels of p-PERK and CHOP in the sciatic nerve tissue of rats in the model group were significantly increased(P<0.05),and the number of apoptosis was significantly increased(P<0.01).The expression levels of this protein in rats in the medium and high dose groups and Western medicine groups were significantly decreased compared with that in the model group,and the number of apoptosis cells was significantly reduced(P<0.05 or P<0.01).Conclusion: Qigui Tangtongning Granules can significantly improve the clinical comprehensive score of DPN patients with deficiency of Qi and Yin combined with stasis,increase the nerve conduction velocity of the affected limb.And its clinical application is safe.The mechanism may be related to the improvement of metabolic disorder,the reduction of AGEs,the reduction of oxidative stress,which leads to the alleviation of ERS,the inhibition of apoptosis of nerve cells,and the improvement of nerve injury. |
