基于Nrf2/HO-1通路研究芹菜素改善妊娠期糖尿病大鼠氧化应激损伤

Study on apigenin improvement of oxidative stress injury in diabetic rats based on Nrf2/HO-1 pathway

目的基于Nrf2/HO-1通路探讨芹菜素对妊娠期糖尿病大鼠氧化应激损伤的影响。方法选用高脂喂养的36只妊娠SD大鼠,腹腔注射链脲佐菌素方法建立妊娠期糖尿病大鼠模型,按照随机数字表法将其分为模型组、芹菜素组(50 mg/kg)、ML385组(Nrf2/HO-1通路抑制剂,剂量为20 mg/kg)、芹菜素+ML385组(芹菜素剂量为50 mg/kg,ML385剂量为20 mg/kg),每组9只。另取9只设为对照组。分组处理后,测量各组大鼠空腹血清血糖(FSG)、三酰甘油(TG)、总胆固醇(TC)水平、肝组织病理变化;检测大鼠血清中白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)水平,肝组织超氧化物歧化酶(SOD)、丙二醛(MDA)水平和Nrf2/HO-1通路蛋白表达。结果与对照组比较,模型组大鼠肝组织呈现结构紊乱,伴有炎症细胞浸润,肝细胞变性、坏死,胞质固缩、深染等病理损伤,FSG、TG、TC、血清中TNF-α及IL-6水平、肝组织MDA水平显著升高(P<0.05),肝组织SOD水平、Nrf2、HO-1蛋白表达显著降低(P<0.05);与模型组比较,ML385组大鼠肝组织病理损伤加重,FSG、TG、TC、血清中TNF-α及IL-6水平、肝组织MDA水平升高(P<0.05),肝组织SOD水平、Nrf2、HO-1蛋白表达降低(P<0.05);与模型组比较,芹菜素组大鼠肝组织病理损伤减轻,FSG、TG、TC、血清中TNF-α及IL-6水平、肝组织MDA水平降低(P<0.05),肝组织SOD水平、Nrf2、HO-1蛋白表达升高(P<0.05);与ML385组比较,芹菜素+ML385组大鼠肝组织病理损伤减轻,FSG、TG、TC、血清中TNF-α及IL-6水平、肝组织MDA水平降低(P<0.05),肝组织SOD水平、Nrf2、HO-1蛋白表达升高(P<0.05)。结论芹菜素可通过激活Nrf2/HO-1通路改善妊娠期糖尿病大鼠氧化应激损伤。

Objective To study the effect of apigenin on oxidative stress injury in gestational diabetic rats based on Nrf2/HO-1 pathway.Methods Thirty-six pregnant SD rats of high-fat feeding were selected,the gestational diabetes rat model was established by intraperitoneal injection of chain urea with cephalosporins method,according to the random number table method they were divided into model group,apigenin group(50 mg/kg),ML385 group(Nrf2/HO-1 pathway inhibitor,dose of 20 mg/kg),apigenin+ML385 group(apigenin dose of 50 mg/kg,ML385 dose of 20 mg/kg),with 9 mice in each group.Another 9 mice were set as the control group.After grouping,the levels of fasting serum blood glucose(FSG),triglyceride(TG),total cholesterol(TC)and pathological changes of liver tissue were measured;the serum levels of interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)were measured,and the levels of superoxide dismutase(SOD),malonic dialdehyde(MDA)and Nrf2/HO-1 pathway protein expression of rats in each group were detected.Results Compared with the control group,the liver tissue of the model group showed structural disorder,accompanied by inflammatory cell infiltration,hepatocyte degeneration,necrosis,cytoplasm contraction,deep staining and other pathological damage,the levels of FSG,TG,TC,serum TNF-αand IL-6,and MDA in liver tissue increased significantly(P<0.05),and SOD level,Nrf2,HO-1 protein expressions in liver tissue were significantly decreased(P<0.05).Compared with the model group,the pathological damage of liver tissue in ML385 group was aggravated,the levels of FSG,TG,TC,serum TNF-αand IL-6,and MDA in liver tissue increased significantly(P<0.05),and SOD level,Nrf2,HO-1 protein expressions in liver tissue were significantly decreased(P<0.05).Compared with the model group,the pathological damage of liver tissue in the apigenin group was alleviated,the levels of FSG,TG,TC,serum TNF-αand IL-6,and MDA in liver tissue decreased significantly(P<0.05),and SOD level,Nrf2 and HO-1 protein expressions in liver tissue were significantly increased(P<0.05).Compared with ML385 group,the pathological damage of liver tissue in apigenin+ML385 group was alleviated,the levels of FSG,TG,TC,serum TNF-αand IL-6,and MDA in liver tissue decreased significantly(P<0.05),and SOD level,Nrf2 and HO-1 protein expressions in liver tissue were significantly increased(P<0.05).Conclusion Apigenin can improve oxidative stress injury in gestational diabetic rats by activating Nrf2/HO-1 pathway.