黄芩苷对妊娠期糖尿病大鼠胰岛素抵抗的影响及机制
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| 篇名: | 黄芩苷对妊娠期糖尿病大鼠胰岛素抵抗的影响及机制 |
| TITLE: | Effects of baicalin on insulin resistance in rats with gestational diabetes mellitus and its mechanism |
| 摘要: | 目的 基于腺苷一磷酸活化蛋白激酶(AMPK)/杂色抑制因子3-9同源物1(SUV39H1)/组蛋白H3第9位赖氨酸三甲基化(H3K9me3)轴,探讨黄芩苷对妊娠期糖尿病(GDM)大鼠胰岛素抵抗的影响及潜在机制。方法采用高脂饮食联合链脲佐菌素注射的方式构建GDM大鼠模型,并将造模成功的大鼠分为GDM组、黄芩苷低剂量组、黄芩苷高剂量组、黄芩苷高剂量+AMPK抑制剂(CompoundC)组,每组10只;另取10只以普通饲料喂养的妊娠大鼠,作为对照组。各组大鼠灌胃和(或)腹腔注射相应药液/生理盐水,每天1次,连续2周。末次给药后,检测各组大鼠的空腹血糖(FBG)、胰岛功能指标[空腹胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)、胰岛素敏感指数(ISI)]、血脂指标(总胆固醇、甘油三酯、低密度脂蛋白胆固醇)、肝功能指标(丙氨酸转氨酶、天冬氨酸转氨酶、碱性磷酸酶)、炎症因子(C反应蛋白、白细胞介素1β、白细胞介素6)、代谢调节蛋白[补体C1q/肿瘤坏死因子相关蛋白3(CTRP3)]、胰岛素敏感性相关因子[葡萄糖转运蛋白4(GLUT4)、脂联素]以及氧化应激指标[超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、丙二醛(MDA)]水平,观察其肝组织病理改变,并检测肝组织中AMPK/SUV39H1/H3K9me3轴相关蛋白的表达情况。结果与GDM组相比,黄芩苷低、高剂量组大鼠肝组织细胞排列紊乱、空泡变性、脂肪沉积、炎症细胞浸润等病理改变均有不同程度改善,其FBG、FINS水平,HOMA-IR,血脂指标、肝功能指标、炎症因子、MDA水平以及SUV39H1、H3K9me3蛋白的表达均显著降低或下调,代谢调节蛋白、胰岛素敏感性相关因子水平和AMPK蛋白的磷酸化水平均显著升高(P<0.05),且黄芩苷高剂量组的改善更显著(P<0.05)。CompoundC可显著逆转高剂量黄芩苷对上述定量指标的改善作用(P<0.05)。结论黄芩苷可显著减轻GDM大鼠的氧化应激和炎症反应,提高体内CTRP3、GLUT4、脂联素水平,从而改善其胰岛素抵抗;上述作用可能与激活AMPK、抑制SUV39H1介导的H3K9me3修饰有关。 |
| ABSTRACT: | OBJECTIVE To investigate the effects of baicalin (BC) on insulin resistance in rats with gestational diabetes mellitus (GDM) and its underlying mechanism based on the adenosine monophosphate-activated protein kinase (AMPK)/suppressor of variegation 3-9 homolog 1 (SUV39H1)/histone H3 lysine 9 trimethylation (H3K9me3) axis. METHODS A GDM rat model was established by a combination of a high-fat diet and streptozotocin injection. The successfully modeled rats were divided into the GDM group, BC low-dose group, BC high-dose group, and high-dose of BC+AMPK inhibitor (Compound C) group, with 10 rats in each group. Another 10 pregnant rats fed a normal diet served as the control group. Rats in each group were given corresponding drugs/normal saline intragastrically and/or intraperitoneally, once daily for 2 consecutive weeks. After the last administration, the levels of fasting blood glucose (FBG), pancreatic function indexes [fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR), insulin sensitivity index (ISI)], blood lipid indexes (total cholesterol, triglyceride, low-density lipoprotein cholesterol), liver function indexes (alanine transferase, aspartate transferase, alkaline phosphatase), inflammatory indicators (C-reactive protein, interleukin-1β, interleukin-6), metabolic regulatory protein [complement-C1q/tumor necrosis factor-related protein 3 (CTRP3)], insulin sensitivity related factors [glucose transporter 4 (GLUT4), adiponectin], and oxidative stress indicators [superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA)] were measured. Pathological changes in liver tissue were observed, and the expressions of proteins related to the AMPK/SUV39H1/H3K9me3 axis in liver tissue were detected. RESULTS Compared with the GDM group, rats in the BC low- and high-dose groups showed varying degrees of improvement in pathological changes such as disordered cell arrangement, vacuolar degeneration, lipid deposition, and inflammatory cell infiltration in liver tissue. Their FBG and FINS levels, HOMA-IR, the levels of blood lipid indexes, liver function indexes, inflammatory indicators and MDA, and the expressions of SUV39H1 and H3K9me3 were significantly decreased or down-regulated, while metabolic regulatory protein, insulin sensitivity-related factors and AMPK protein phosphorylation levels were significantly increased ( P <0.05). The improvement was more significant in the BC high-dose group ( P <0.05). Compound C could significantly reverse the ameliorative effects of high-dose BC on the above quantitative indicators ( P <0.05). CONCLUSIONS BC can significantly reduce oxidative stress and inflammatory responses, increase serum levels of CTRP3, GLUT4 and adiponectin, thereby improving insulin resistance in GDM rats. These effects may be related to the activation of AMPK and inhibition of SUV39H1-mediated H3K9me3 modification. |
| 期刊: | 2026年第37卷第04期 |
| 作者: | 石克威;陈曦;赵晓燕;杨博;刘云春;高月月 |
| AUTHORS: | SHI Kewei,CHEN Xi,ZHAO Xiaoyan,YANG Bo,LIU Yunchun,GAO Yueyue |
| 关键字: | 黄芩苷;妊娠期糖尿病;胰岛素抵抗;AMPK/SUV39H1/H3K9me3轴 |
| KEYWORDS: | baicalin; gestational diabetes mellitus; insulin resistance; AMPK/SUV39H1/H3K9me3 axis |
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