目的 探讨葛根芩连汤对妊娠糖尿病(GDM)小鼠模型的作用及其机制.方法 以C57BLKsJdb/+(db/+)怀孕小鼠建立遗传性GDM小鼠模型,空白组采用C57BL/KsJ+/+(野生型)怀孕小鼠作为对照,将模型小鼠随机分为模型组,葛根芩连汤低(15g/kg)、高剂量组(45 g/kg)和阳性药物组(二甲双胍,200 mg/kg),每组10只.给药处理组小鼠自妊娠日开始给药,空白组和模型组给予等量生理盐水.检测葛根芩连汤对GDM小鼠及其子代的安全性的影响,检测GDM小鼠糖耐量和胰岛素耐量、血清和胰腺组织中胰岛素水平,采用组织切片观察胰岛病理学变化,RT-PCR检测胰腺组织中胰岛素生成和分泌相关因子的转录水平;检测Min6细胞的增殖、Min6细胞在高糖刺激下的胰岛素分泌量.结果 与模型小鼠比较,葛根芩连汤组及阳 性药物组小鼠肝脏和肾脏的病理学形态得以改善;与模型组小鼠比较,GDM给药葛根芩连汤小鼠的糖耐量和胰岛素耐量显著改善(P＜0.05)、胰岛形态显著改善、血清和胰腺组织中胰岛素水平升高、胰岛素生成和分泌相关因子的转录水平显著上调(P＜0.01,P＜0.05);进一步机制研究发现葛根芩连汤可下调p38蛋白的磷酸化水平,上调多囊肾病1型致病基因(PKD1)蛋白的磷酸化水平(P＜0.01,P＜0.05).在Min6细胞模型中,葛根芩连汤可促进Min6细胞的增殖,促进Min6细胞在高糖刺激下的胰岛素分泌量(P＜0.01).采用工具药阻断发现抑制了 PKD1之后,减弱了葛根芩连汤对胰岛素的升高作用(P＜0.01).结论 葛根芩连汤对GDM小鼠及其子代的安全性良好,可通过调控p38-PKD1信号通路而促进胰岛素分泌,对妊娠糖尿病具有一定的干预作用.
Objective To investigate the effects and mechanisms of Gegen Qinlian Decoction(GGQLD)on a mouse model of gestational diabetes mellitus(GDM).Methods A genetic GDM mouse model was established using C57BL//KsJdb/+(db/+)pregnant mice,while C57BUKsJ+/+(wild-type)pregnant mice were used as controls.The model mice were randomly divided into the model group,low-dose GGQLD group,high-dose GGQLD group,and positive drug group(metformin),with 10 mice in each group.The treatment groups received treatment from the day of pregnancy,while the control and model groups were administered an equivalent amount of physiological saline.The study assessed the safety of GGQLD on GDM mice and their offspring,examining glucose tolerance,insulin tolerance,insulin levels in serum and pancreatic tissue,pancreatic histopathological changes through tissue sections,and the transcription levels of insulin generation and secretion-related factors in pancreatic tissue using RT-PCR.Additionally,cell proliferation in Min6 cells,as well as insulin secretion under high-glucose stimulation,were evaluated.Results Compared with the GDM model mice,the pathological morphology of the liver and kidneys in the GGQLD and positive drug groups improved.Compared with model group,GDM mice treated with GGQLD showed significant improvements in glucose tolerance and insulin tolerance(P＜0.05),marked improvement in pancreatic morphology,increased insulin levels in serum and pancreatic tissue,and upregulation of transcription levels of insulin generation and secretion-related factors(P＜0.01,P＜0.05).Further mechanistic studies revealed that GGQLD could downregulate the phosphorylation level of p38 protein and upregulate the phosphorylation level of polycystic kidney disease gene 1(PKD1)protein(P＜0.01,P＜0.05).In the Min6 cell model,GGQLD promoted cell proliferation and insulin secretion under high-glucose stimulation(P＜0.01).Using a pharmacological tool to block PKD1,it was found that inhibiting PKD1 weakened the elevating effect of GGQLD on insulin(P＜0.01).Conclusion GGQLD demonstrates good safety for GDM mice and their offspring,and it promotes insulin secretion by regulating the p38-PKD1 signaling pathway,suggesting a potential therapeutic effect on gestational diabetes mellitus.
王琳琳;胡可佳
北京中医医院顺义医院妇产科(北京 101300)
葛根芩连汤;安全性;妊娠糖尿病;胰岛素分泌;多囊肾病1型致病基因蛋白;p38-PKD1信号通路;中药复方
Gegen Qinlian Decoction;safety;gestational diabetes mellitus;insulin secretion;polycystic kidney disease gene 1 protein;p38-PKD1 signaling pathway;Chinese herbal compound
《中国中西医结合杂志》 2024 (005)
567-574 / 8
北京中医医院顺义医院院级自然基金项目(No.SYYJ-201906)
10.7661/j.cjim.20240315.065
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