运脾和络汤调控SIRT1-FoxO1通路改善2型糖尿病大鼠胰腺脂肪异位沉积的研究

Study on the Yunpi Heluo Decoction in inhibiting pancreatic ectopic fat deposition in type 2 diabetic mellitus rats via SIRT1-FoxO1 pathway

目的:探讨运脾和络通过SIRT1-FoxO1通路改善2型糖尿病(T2DM)大鼠胰腺脂肪异位沉积。方法:ZL大鼠普通饲料喂养作为空白对照组,ZDF大鼠高脂饲料喂养4周造模成功后,随机分为模型组、给药组、SIRT1空载组(空载组)和SIRT1过表达组(过表达组)。给药组用运脾和络汤灌胃干预8周。空载组与过表达组予腺相关病毒尾静脉一次性注射。8周干预结束后各组大鼠取血进行相关生化检测,取空白对照组、模型组、给药组大鼠胰腺组织运用HE染色和油红O染色进行镜下观察;取5组大鼠胰腺组织运用qPCR和Western Blot分别检测SIRT1、FoxO1mRNA和蛋白表达。结果:与模型组比较,给药组胰腺组织脂肪空泡减少,给药组和过表达组SIRT1蛋白表达升高(P<0.01)、FoxO1蛋白表达降低(P<0.01);与空载组比较,过表达组相关生化指标(FBG、FINS、HOMA-IR、血脂四项)改善(P<0.01),SIRT1 mRNA表达升高(P<0.01),FoxO1蛋白表达降低(P<0.01)。结论:运脾和络汤能改善胰腺组织脂肪异位沉积,该作用可能与SIRT1-FoxO1通路相关。

Objective: To investigate the effects of Yunpi Heluo Decoction on pancreatic fat deposition in type 2 diabetic mellitus(T2 DM) rats by SIRT1-FoxO1 pathway. Methods: ZL rats fed with normal diet were as blank control group. ZDF rats fed with high-fat diet for 4 weeks and model establishment were randomly divided into model group, administration group, SIRT1 empty group and SIRT1 overexpression group. The treatment group was given Yunpi Heluo Decoction for 8 weeks. SIRT1 empty group and SIRT1 overexpression group were injected with adeno-associated virus via tail vein. After 8 weeks of intervention, blood samples were collected for biochemical detection. Pancreatic tissues of blank control group, model group and administration group were observed under microscope with HE staining and oil red O staining;the expression of SIRT1-FoxO1 pathway related proteins was detected by qPCR and Western Blot. Results: Compared with the model group, the number of fat vacuoles in pancreatic tissue in the treatment group decreased, the expression of SIRT1 increased and the expression of FoxO1 decreased in the treatment group and SIRT1 overexpression group(P<0.01);compared with the SIRT1 empty group, the related biochemical indexes(FBG, FINS, HOMA-IR, four item of blood lipids) in the SIRT1 overexpression group were improved(P<0.01), the mRNA expression of SIRT1 was increased, and the protein expression of FoxO1 was decreased(P<0.01). Conclusion: Yunpi Heluo Decoction can improve the ectopic fat deposition in pancreas, which may be related to SIRT1-FoxO1 pathway.