【摘要】 目的探讨冬虫夏草（CS）-4提取物对他克莫司（TAC）所致胰腺和肾脏损伤的保护作用及分子机制。方法雄性Sprague-Dawley（SD）大鼠皮下注射TAC(1.5 mg·kg^-1·d^-1)建立TAC肾毒性模型16只,肾毒性模型中随机选8只大鼠给予CS治疗(5 g·kg^-1·d^-1,灌胃)4 w。检测大鼠的血糖、胰岛素水平、肾功能、24 h尿蛋白排泄率、8-羟基脱氧鸟苷（8OHdG）;采用免疫组化和免疫印迹法分别检测胰腺胰岛素、炎性介质、致纤因子、细胞凋亡相关基因的表达。结果CS明显减少胰腺细胞凋亡、保护胰岛数量,其结果是血糖下降和胰岛素水平上升;此外,CS改善肾功能和肾小管间质纤维化,减少尿蛋白排泄率和血尿8-OHdG水平。在分子水平上,CS下调炎性介质和致纤因子的表达,调节细胞凋亡调控基因的表达。结论 CS对TAC诱导的胰腺和肾脏损伤具有降糖、抗炎、抗纤维化等保护作用。更多还原

【Abstract】 Objective To assess the beneficial effects of Cordyceps sinensis( CS) on pancreatic and renal injury in an experi-mental model of tacrolimus( TAC)-induced diabetes mellitus.Methods Sprague-Dawley rats were given daily TAC( 1.5 mg/kg,sub-cutaneously) and CS( 5 g/kg,oral gavage) for 4 weeks. The influence of CS on pancreatic injury was studied by examining intraperito-neal glucose tolerance test,plasma insulin concentration,glucose-stimulated insulin secretion and intact pancreatic islet size. In addi-tion,the renoprotective effects of CS were assessed in terms of renal function,urine albumin excretion,histopathology,expression ofproinflammatory and profibrotic cytokines,oxidative stress and apoptotic cell death.Results CS treatment abrogated pancreatic cell ap-optosis and preserved pancreatic islet size,followed by a significant decrease in blood glucose level and an increase in plasma insulinlevel,as well as glucose-stimulated insulin secretion. In the kidney,CS improved renal dysfunction and reduced albumin excretion andhistological injury,which was paralleled by suppression of profibrotic cytokine and proinflammatory mediator expression. Enhanced oxi-dative stress and apoptotic cell death induced by TAC were dramatically decreased with administration of CS.Conclusions CS is capa-ble of governing TAC-associated hyperglycemia and has a renoprotective effect on TAC-induced renal injury.更多还原