Effect of Zhuang-medicine medicated thread moxibustion on apoptosis-related protein expression in gastric smooth muscle tissue of diabetic gastroparesis rats based on ATF6/CHOP signaling pathway

WU Yu ,  

FAN Yu-shan ,  

WANG Zi-bin ,  

XU Hui ,  

ZHANG Fang-zhi ,  

MIAO Fu-rui ,  

HE Yu-jun ,  

MAI Wei ,  

摘要

ObjectiveTo 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.MethodsMale 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, with 12 rats in each group. The DGP model was established by intraperitoneal injection of 2% streptozotocin (STZ, 55mg/kg). Rats of the medication group received gavage of Mosapride Citrate suspension (0.15mg/mL). For rats in the Yangming meridian acupoint moxibustion group, the medicated thread moxibustion was applied to bilateral Liangmen (ST 21), Qichong (ST 30), Zusanli (ST 36) and Fenglong (ST 40), with three moxa cones for each acupoint. For rats of the non-meridian non-acupoint group, the same medicated thread moxibustion was applied to the sites 2.5mm or 5mm away from the abovementioned Yangming meridian acupoints. The 3 intervention groups were conducted once daily for 3 weeks. The symptom score of mental behavior, hair gloss, weight change, diet and drinking water, urine and feces dehydration 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 was detected using western blot, and the immunoactivity of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), and caspase-12 in the gastric smooth muscle tissues was detected using immunohistochemistry method.ResultsCompared to the control group, rats in the model group exhibited a significant increase in the symptom scores, 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), but not by non-acupoint moxibustion (P>0.05). 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), while the gastric emptying rate and expression of Bcl-2 significantly higher in the latter group than in the former group (P<0.01).ConclusionZhuang-medicine acupoint 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.

关键词

Zhuang-medicine medicated thread moxibustion;Diabetic gastroparesis;Endoplasmic reticulum stress;ATF6/CHOP signaling pathway;Apoptosis;Gastric emptying function

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