文献类型：期刊文献

中文题名：基于ATF6/CHOP通路的红芪多糖对糖尿病胃轻瘫大鼠胃窦组织平滑肌的影响

英文题名：Effects of Hedysarum Polybotrys Polysaccharide on the Smooth Muscle of Gastric Antrum Tissue in Diabetic Gastroparesis Rats Based on ATF6/CHOP Pathway

作者：李林江[1];万生芳[1];李荣科[1];张磊[1];杨雅丽[1];张亚男[1];荀敏奇[1]

第一作者：李林江

机构：[1]甘肃中医药大学,甘肃兰州730000

第一机构：甘肃中医药大学

年份：2022

卷号：29

期号：11

起止页码：67

中文期刊名：中国中医药信息杂志

外文期刊名：Chinese Journal of Information on Traditional Chinese Medicine

收录：CSTPCD;;CSCD:【CSCD_E2021_2022】；

基金：国家自然科学基金(82060914、81560718);甘肃省中医药管理局科研课题(GZK-2017-3)。

语种：中文

中文关键词：红芪多糖;糖尿病胃轻瘫;细胞凋亡;内质网应激;ATF6/CHOP通路;大鼠

外文关键词：Hedysarum polybotrys polysaccharide;diabetic gastroparesis;apoptosis;endoplasmic reticulum stress;ATF6/CHOP pathway;rats

摘要：目的观察红芪多糖对糖尿病胃轻瘫(DGP)大鼠胃窦组织平滑肌的影响,从ATF6/CHOP信号通路探讨其作用机制。方法72只Wistar雄性大鼠随机分为空白组12只、造模组60只,造模组采用一次性腹腔注射链脲佐菌素50 mg/kg和高糖高脂饲料不规则喂食4周复制DGP模型。将成模大鼠随机分为模型组、二甲双胍组和红芪多糖高、中、低剂量组。红芪多糖高、中、低剂量组分别予红芪多糖药液200、100、50 mg/kg灌胃,二甲双胍组予二甲双胍药液200 mg/kg灌胃,每日1次,连续4周。每2周测定大鼠随机血糖,检测胃排空率,TUNEL染色检测胃窦组织平滑肌细胞凋亡率,Westernblot检测胃窦组织平滑肌葡萄糖调节蛋白78(GRP78)、活化转录因子6(ATF6)、CCAAT增强子结合蛋白同源蛋白(CHOP)、半胱氨酸蛋白酶-12(Caspase-12)表达,免疫组化染色检测胃窦组织平滑肌GRP78、ATF6、CHOP、Caspase-12、Bcl-2、Bax蛋白表达。结果与空白组比较,模型组大鼠第0、2、4周血糖升高,胃排空率降低;胃窦组织平滑肌细胞凋亡率升高,GRP78、ATF6、CHOP、Caspase-12、Bax蛋白表达升高,Bcl-2蛋白表达降低,差异均有统计学意义(P<0.01)。与模型组比较,红芪多糖高、中剂量组和二甲双胍组大鼠第2、4周血糖降低,胃排空率升高;胃窦组织平滑肌细胞凋亡率降低,GRP78、ATF6、CHOP、Caspase-12蛋白表达降低,Bcl-2蛋白表达升高,差异均有统计学意义(P<0.05,P<0.01)。结论红芪多糖可能通过抑制ATF6/CHOP通路相关蛋白表达减轻DGP模型大鼠胃窦组织平滑肌细胞凋亡,进而缓解DGP进展。
Objective To investigate the effects of Hedysarum polybotrys polysaccharide on the smooth muscle of gastric antrum tissue in diabetic gastroparesis(DGP)rats;To explore the mechanism from ATF6/CHOP pathway.Methods Totally 72 Wistar male rats were randomly divided into blank group(12 rats)and modeling group(60 rats).The rats in the modeling group were injected with streptozotocin(50 mg/kg)intraperitoneally and fed irregularly with high-sugar and high-fat diet for 4 weeks to replicate DGP model.After modeling,they were randomly divided into model group,metformin group and Hedysarum polybotrys polysaccharide high,medium-and low-dosage groups.The Hedysarum polybotrys polysaccharide high-,medium-and low-dosage groups were given 200,100 and 50 mg/kg Hedysarum polybotrys polysaccharide solution for gavage,and the metformin group was given 200 mg/kg metformin solution for gavage,once a day,for consecutive 4 weeks.Random blood glucose measurements were performed every two weeks,gastric emptying rate was detected,the apoptosis rate of smooth muscle cells in gastric antrum was detected by TUNEL staining,the expressions of GRP78,ATF6,CHOP and Caspase-12 in smooth muscle of gastric antrum were detected by Western blot,immunohistochemical staining was used to detect the expressions of GRP78,ATF6,CHOP,Caspase-12,Bcl-2 and Bax protein in smooth muscle of gastric antrum.Results Compared with the blank group,the blood glucose of the rats in model group increased,the gastric emptying rate decreased;the apoptosis rate of smooth muscle cells in gastric antrum tissue increased,the expression of GRP78,ATF6,CHOP,Caspase-12,Bax protein increased,and the expression of Bcl-2 protein decreased,all with statistical significance(P<0.01).Compared with the model group,the blood glucose of the rats in Hedysarum polybotrys polysaccharide high-,midium-dosage group and metformin group decreased,the gastric emptying rate increased;the apoptosis rate of smooth muscle cells in gastric antrum tissue decreased,the proteins expression of GRP78,ATF6,CHOP,Caspase-12 and Bax decreased,and the expression of Bcl-2 protein increased,all with statistical significance(P<0.05,P<0.01).Conclusion Hedysarum polybotrys polysaccharide can reduce the apoptosis of smooth muscle cells in gastric antrum tissue of DGP rats by inhibiting the expression of ATF6/CHOP pathway related protein,thus alleviating the progression of DGP.