西罗莫司对慢性轻度不可预知应激大鼠线粒体自噬的影响

Effect of sirolimus on mitophagy in chronic unpredictable mild stress rats

目的探究西罗莫司对慢性轻度不可预知应激(chronic unpredictable mild stress,CUMS)大鼠行为学和海马区线粒体自噬的影响。方法SD大鼠经过蔗糖偏好率基线测试后,随机分为空白组8只和造模组30只。造模组给予3周的CUMS造模处置,造模成功的大鼠随机分为模型组8只、对照组9只和实验组9只。空白组和模型组均灌胃给予10 mL·kg^(-1)·d^(-1)0.9%NaCl;对照组灌胃给予10 mL·kg^(-1)·d^(-1)氟西汀;实验组给予腹腔注射10 mL·kg^(-1)·d^(-1)西罗莫司。4组大鼠均干预3周,给药同时继续造模。用蔗糖偏好实验检测蔗糖偏好率变化,用蛋白质印迹法检测磷酸酶及张力蛋白同源物诱导激酶1(PTEN Induced putative kinase 1,PINK-1)和Parkin的表达情况。结果实验组、对照组、模型组和空白组大鼠的蔗糖偏好率分别为0.65±0.06,0.71±0.08,0.41±0.09和0.77±0.08,PINK-1蛋白相对表达水平分别为0.55±0.01,0.62±0.01,0.45±0.01和0.68±0.03,Parkin蛋白相对表达水平分别为0.83±0.01,0.88±0.02,0.57±0.02和0.69±0.02。实验组的上述指标与模型组比较,差异均有统计学意义(均P<0.01)。结论西罗莫司可改善CUMS大鼠蔗糖偏好率,其机制可能与调控PINK-1/Parkin通路介导的线粒体自噬有关。

Objective To study the effects of sirolimus on the behavior and hippocampal mitophagy in rats with chronic unpredictable mild stress(CUMS)depression.Methods After sucrose preference tests,rats were randomly divided into blank group(n=8 cases)and modeling group(n=30 cases).After 3 weeks of CUMS modeling,the successful model rats were randomly divided into model group(n=8 cases),control group(n=9 cases)and experimental group(n=9 cases).Blank group and model group were given 10 mL·kg^(-1)·d^(-1)0.9%NaCl by gavage.Control group was given 10 mL·kg^(-1)·d^(-1)fluoxetine by gavage.Experimental group received intraperitoneal injection of 10 mL·kg^(-1)·d^(-1)sirolimus.Four groups were intervened for 3 weeks and continued to modeling.The sucrose preference rates of rats were observed,the expressions of PTEN induced putative kinase 1(PINK-1)and Parkin were detected with Western blot.Results The sucrose preference rates of experimental,control,model and blank groups were 0.65±0.06,0.71±0.08,0.41±0.09 and 0.77±0.08;the expression levels of PINK-1 were 0.55±0.01,0.62±0.01,0.45±0.01 and 0.68±0.03;the expression levels of Parkin were 0.83±0.01,0.88±0.02,0.57±0.02 and 0.69±0.02.There above indexes were statistically significant between experimental group and model group(all P<0.01).Conclusion Sirolimus could improve the sucrose preference rate of CUMS rats,which may be related to the regulation of mitophagy mediated by PINK-1/Parkin pathway.