基于ATF6/CHOP通路探究壮医药线点灸对糖尿病胃轻瘫大鼠胃平滑肌组织凋亡相关蛋白表达的影响OA

Objective To observe the effect of Zhuang-medicine medicated thread moxibustion on endoplasmic reticulum stress-associated apoptotic proteins in rats with diabetic gastroparesis(DGP),so as to explore its underlying therapeutic mechanisms.Methods Male SD rats were randomly divided into five groups:blank control,DGP model,medication,non-meridian non-acupoint(non-acupoint)moxibustion,and Yangming meridian acupoint moxibustion groups,with 12 rats in each group.The DGP model was established by intraperitoneal injection of 2%streptozotocin(STZ,55 mg/kg).Rats of the medication group received gavage of mosapride citrate suspension(0.15 mg/mL).For rats in the Yangming meridian acupoint moxibustion group,the medicated thread moxibustion was applied to bilateral"Liangmen"(ST21),"Qichong"(ST30),"Zusanli"(ST36)and"Fenglong"(ST40),with three moxa cones for each acupoint.For rats of the non-acupoint group,the same medicated thread moxibustion was applied to the sites 2.5 mm or 5 mm away from the abovementioned Yangming meridian acupoints.The 3 intervention groups were conducted once daily for 3 weeks.The symptom scores were assessed.The blood glucose levels were measured using a blood glucose meter,and the gastric emptying rate was assessed by using phenol red gavage method.The apoptosis index of gastric smooth muscle cells was detected using TUNEL staining.The expression levels of glucose-regulated protein 78(GRP78),activating transcription factor 6(ATF6),and CCAAT/enhancer-binding protein homologous protein(CHOP)in the gastric antral smooth muscle were detected using Western blot,and the immunoactivities of B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),and Caspase-12 in the gastric smooth muscle tissues were detected using immunohistochemistry method.Results Compared to the control group,rats in the model group exhibited a significant increase in the symptom score,blood glucose level,smooth muscle cell apoptosis index,and the expression levels of GRP78,ATF6,CHOP,Bax and Caspase-12 proteins(P<0.01),and an obvious decrease in the gastric emptying rate and expression of Bcl-2 protein(P<0.01).In contrast to the model group,both the significant increase and decrease of the indexes mentioned above were all reversed by Yangming acupoint moxibustion and medication(P<0.01,P<0.05),but not by non-acupoint moxibustion,except blood glucose level which was only decreased in the Yangming acupoint moxibustion group(P<0.01).Comparison between the Yangming meridian acupoint group and non-acupoint group displayed that the symptom score,blood glucose,apoptosis index,and expression of GRP78,ATF6,CHOP,Bax and Caspase-12 proteins were significantly higher in the latter group than in the former group(P<0.01,P<0.05),while the gastric emptying rate and expression of Bcl-2 were significantly lower in the latter group than in the former group(P<0.01).Conclusion Zhuang-medicine medicated thread moxibustion can ameliorate symptoms,promote gastric emptying and lower blood glucose in DPG rats,which may be related to its functions in regulating the expression of endoplasmic reticulum stress-associated apoptotic proteins,suppressing the expression of GRP78,ATF6,CHOP,Caspase-12,and Bax proteins(ATF6/CHOP signaling pathway)and upregulating the expression of Bcl-2 protein in the gastric antral smooth muscle.