丹瓜方调控SIRT1/PGC-1α通路对2型糖尿病大鼠肝脏损伤的影响研究OA
Dangua decoction ameliorates hepatic injury in rats with type 2 diabetes mellitus via regulating the SIRT1/PGC-1α pathway
目的 探讨丹瓜方对 2 型糖尿病(T2DM)大鼠肝脏损伤及沉默信息调节因子 1(SIRT1)/过氧化物酶体增殖物激活受体 γ 共激活因子1α(PGC-1α)通路的调控作用.方法 取20 只雄性 SD 大鼠,随机选5 只作为正常组,其余大鼠采用喂养高糖高脂饲料及腹腔注射1%链脲佐菌素溶液方法建立 T2DM 模型.将造模成功大鼠随机分为模型组、丹瓜方组和二甲双胍组,每组5 只.正常组和模型组按照10 mL/kg 剂量灌胃无菌水,丹瓜方组按照20 g/kg 剂量灌胃丹瓜方药液,二甲双胍组按照0.11 g/kg 剂量灌胃二甲双胍药液,均1 次/d,连续灌胃14 周.检测各组大鼠空腹血糖(FPG)、餐后2h 血糖(2hPG)、糖化血红蛋白(HbA1c)及血清总胆固醇(TC)、三酰甘油(TG)、丙二醛(MDA)、白细胞介素-6(IL-6)水平,HE 和 Masson 染色观察肝脏病理组织形态,Western blot 法检测肝脏组织中 SIRT1 和 PGC-1α 蛋白表达情况.结果 与正常组比较,模型组大鼠 FPG、2hPG、HbA1c、TC、TG、MDA 和 IL-6 水平均明显升高(P 均<0.05);肝小叶结构紊乱,大量炎性细胞浸润,胶原纤维增多;肝脏组织中 SIRT1 和 PGC-1α 蛋白相对表达量均明显降低(P均<0.05).与模型组比较,丹瓜方组和二甲双胍组大鼠 FPG、2hPG、HbA1c、TC、TG、MDA 和 IL-6水平均明显降低(P 均<0.05);肝脏病理损伤明显减轻;肝脏组织中 SIRT1 和 PGC-1α 蛋白相对表达量均明显升高(P 均<0.05).结论 丹瓜方可改善 T2DM 大鼠肝脏损伤,机制可能与调控肝脏 SIRT1/PGC-1α 通路,减轻氧化应激与炎症反应有关.
Objective It is to explore the regulatory effects of Dangua decoction(DGD)on hepatic injury and the silent information regulator 1(SIRT1)/peroxisome proliferator-activated receptor gamma coactivator 1α(PGC-1α)pathway in the rats with type 2 diabetes mellitus(T2DM).Methods Twenty male SD rats were selected,5 of which were randomly as-signed to the control group,while the remaining rats were fed with a high-sugar,high-fat diet and given 1%streptozotocin solution via intraperitoneal injection to establish T2DM modes.The successfully modeled rats were randomly divided into model group,DGD group and metformin group,with 5 rats in each group.The normal group and model group were admin-istered sterile water at a dose of 10 mL/kg via gavage,the DGD group was administered DGD solution at a dose of 20 g/kg via gavage,and the metformin group was administered metformin solution at a dose of 0.11 g/kg via gavage,all once daily,continuously treated for 14weeks.The levels of fasting plasma glucose(FPG),2 h postprandial glucose(2hPG),glycated hemoglobin(HbA1c),total cholesterol(TC),triglycerides(TG),malondialdehyde(MDA)and interleukin-6(IL-6)in serum of rats of each group were measured,the liver histopathology was observed by HE staining and Masson's staining,and the protein expressions of SIRT1 and PGC-1α in liver tissue were decocted by Western blot.Results Compared with the control group,the levels of FPG,2hPG,HbA1c,TC,TG,MDA and IL-6 in serum of rats in the model group were signifi-cantly increased(all P<0.05);the liver lobule structure was disrupted with extensive inflammatory cell infiltration and in-creased collagen fibers;the relative protein expressions of SIRT1 and PGC-1α in liver tissue were significantly reduced(all P<0.05).Compared with the model group,the levels of FPG,2hPG,HbA1c,TC,TG,MDA and IL-6 in serum of rats in the DGD group and metformin group were significantly decreased(all P<0.05);the liver histopathological injury was ameliorated;the relative protein expressions of SIRT1 and PGC-1α in liver tissue were significantly increased(all P<0.05).Conclusion DGD may ameliorate hepatic injury in T2DM rats via regulating the hepatic SIRT1/PGC-1α pathway,thereby reducing oxidative stress and inflammatory responses.
林妍彦;王志塔;韩壮;陈奇炜;靳霖溪;洪鑫淼;衡先培;杨柳清;李亮;何卫东
福建中医药大学附属人民医院,福建 福州 350004||福建中医药大学,福建 福州 350122福建中医药大学附属人民医院,福建 福州 350004福建中医药大学附属人民医院,福建 福州 350004||福建中医药大学,福建 福州 350122福建中医药大学附属人民医院,福建 福州 350004||福建中医药大学,福建 福州 350122福建中医药大学附属人民医院,福建 福州 350004||福建中医药大学,福建 福州 350122福建中医药大学附属人民医院,福建 福州 350004||福建中医药大学,福建 福州 350122福建中医药大学附属人民医院,福建 福州 350004福建中医药大学附属人民医院,福建 福州 350004福建中医药大学附属人民医院,福建 福州 350004福建中医药大学附属人民医院,福建 福州 350004
医药卫生
丹瓜方2型糖尿病沉默信息调节因子1过氧化物酶体增殖物激活受体γ共激活因子1α肝脏损伤
Dangua decoctiontype 2 diabetes mellitusSIRT1PGC-1αhepatic injury
《现代中西医结合杂志》 2026 (12)
1632-1636,1643,6
国家自然科学基金资助项目(82574894,82274389,82205071)福建省科技创新联合资助项目(2025Y9560,2025Y9571)
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