文献类型：期刊文献

中文题名：基于cAMP/PKA信号通路探讨红芪多糖影响糖尿病胃轻瘫大鼠钙稳态和能量代谢的作用机制

英文题名：Hongqi(红芪)Polysaccharide Regulates Calcium Homeostasis and Energy Metabolism in Rat Model of Diabetic Gastroparesis via cAMP/PKA Signaling Pathway

作者：安惠[1,2];朱小利[1,2];魏昭晖[1];李荣科[1];张磊[1];苗琳琳[1,2];万生芳[1]

第一作者：安惠

机构：[1]甘肃中医药大学,兰州730000;[2]甘肃省中医方药挖掘与创新转化重点实验室,兰州730000

第一机构：甘肃中医药大学

年份：2024

卷号：40

期号：8

起止页码：56

中文期刊名：中药药理与临床

外文期刊名：Pharmacology and Clinics of Chinese Materia Medica

收录：;北大核心:【北大核心2023】；CSCD:【CSCD2023_2024】；

基金：国家自然科学基金(编号:82060914)。

语种：中文

中文关键词：红芪多糖;糖尿病胃轻瘫;环磷酸腺苷/蛋白激酶A信号通路;钙稳态;能量代谢

外文关键词：Hongqi(红芪)polysaccharide;Diabetic gastroparesis;Cyclic adenosine monophosphate(cAMP)/protein kinase A(PKA)signaling pathway;Calcium homeostasis;Energy metabolism

摘要：目的:探究红芪多糖对糖尿病胃轻瘫(Diabetic gastroparesis,DGP)大鼠钙稳态和能量代谢的作用机制。方法:62只雄性Wistar大鼠随机分为正常对照组12只和造模组50只,采用小剂量多次注射链脲佐菌素+不规则饮食复制DGP模型。将成模大鼠随机分为模型对照组、莫沙必利1.35 mg/kg组和红芪多糖50、100、200 mg/kg组,各给药组给予相应药物灌胃,正常对照组和模型对照组予等体积纯净水灌胃。观察大鼠一般情况,称体质量、检测随机血糖、胃排空率;HE染色观察大鼠胃窦组织病理改变;ELISA法检测胃窦组织中ATP、Na^(+)-K^(+)ATP酶、Ca^(2+)-Mg^(2+)ATP酶、钙离子(Ca^(2+))浓度;免疫组化和Western blot法分别检测胃窦组织中环磷酸腺苷(cAMP)、蛋白激酶A(PKA)、钙调蛋白依赖蛋白激酶Ⅱ(CaMKⅡ)及其磷酸化的分布和蛋白表达。结果:与正常对照组相比,模型对照组大鼠体质量、胃排空率和胃窦组织中ATP、Na^(+)-K^(+)ATP酶和Ca^(2+)-Mg^(2+)ATP酶浓度、cAMP和PKA蛋白表达均显著降低(P<0.01),血糖、胃窦组织中Ca^(2+)浓度和CaMKII及其磷酸化蛋白表达升高(P<0.01);与模型组对照相比,各给药组大鼠的体质量、胃排空率,胃窦组织中ATP、Na^(+)-K^(+)ATP酶和Ca^(2+)-Mg^(2+)ATP酶浓度、cAMP、PKA蛋白表达均明显升高(P<0.05或P<0.01),血糖、胃窦组织中Ca^(2+)浓度和CaMKII及其磷酸化蛋白表达均明显降低(P<0.05或P<0.01)。结论:HPS可以调节DGP大鼠钙稳态促进能量代谢,其机制可能与上调cAMP/PKA信号通路的表达,抑制CaMKII活性有关。
Objective:To explore the mechanism of Hongqi(红芪)polysaccharide(HPS)in regulating the calcium homeostasis and energy metabolism in the rat model of diabetic gastroparesis(DGP).Methods:Sixty-two male Wistar rats were randomized into a blank group(n=12)and a modeling group(n=50).The DGP model was established by multiple injections of streptozotocin combined with feeding with an irregular diet.The modeled rats were randomized into model control,mosapride(1.35 mg/kg),and HPS(200,100,and 50 mg/kg)groups.The rats in each group were administrated with corresponding drugs by gavage,while those in the blank and model control groups were administrated with equal volumes of pure water by gavage.The general conditions of rats were observed,and the body mass,random blood glucose,and gastric emptying rate were measured.Hematoxylin-eosin staining was conducted to observe the pathological changes of the gastric antrum tissue in rats.Enzyme-linked immunosorbent assay was employed to measure the levels of ATP,Na^(+)-K^(+)ATPase,Ca^(2+)-Mg^(2+)ATPase,and calcium ion(Ca^(2+))in the gastric antrum tissue.Immunohistochemistry and Western blotting were respectively employed to detect the distribution and determine the protein levels of cyclic adenosine monophosphate(cAMP),protein kinase A(PKA),calmodulin-dependent protein kinase II(CaMKII),and their phosphorylated forms in the gastric antrum tissue.Results:Compared with the blank group,the model control group showed decreased body mass and gastric emptying rate,lowered levels of ATP,Na^(+)-K^(+)ATPase,and Ca^(2+)-Mg^(2+)ATPase,down-regulated protein levels of cAMP and PKA,elevated blood glucose and Ca^(2+)levels,and up-regulated protein levels of CaMKII and its phosphorylated form in the gastric antrum tissue(P<0.01).Compared with the model control group,drug interventions increased the body weight and gastric emptying rate,elevated the levels of ATP,Na^(+)-K^(+)ATPase,and Ca^(2+)-Mg^(2+)ATPase,up-regulated the protein levels of cAMP and PKA,lowered the blood glucose and Ca^(2+)levels,and down-regulated the protein levels of CaMKII and its phosphorylated form in the gastric antrum tissue(P<0.05 or P<0.01).Conclusion:HPS can regulate calcium homeostasis and promote energy metabolism in DGP rats by up-regulating the expression of cAMP/PKA signaling pathway and inhibiting CaMKII activity.