小热休克蛋白家族和自噬相关蛋白在自发性2型糖尿病db/db小鼠海马组织中的表达

Expression of small heat shock protein family and autophagy related proteins in the hippocampus of db/db mice with spontaneous type 2 diabetes

目的观察自发性2型糖尿病db/db小鼠海马组织中小热休克蛋白家族(sHSPs)及自噬相关蛋白表达情况。方法正常db/m小鼠作为对照组,糖尿病db/db小鼠作为模型组,各10只。观察其体质量,空腹血糖(FBG);real-time PCR检测海马组织中小热休克蛋白家族、自噬相关基因mRNA的表达;Western blot检测HSPB8、BAG3、LC3、P62蛋白表达。结果1)db/db小鼠体质量、空腹血糖均明显高于db/m小鼠(P<0.01)。2)小热休克蛋白1-10(heat shock protein family B[small]member 1-10,HSPB 1-10)基因mRNA在小鼠海马组织中均有表达;其中HSPB1、HSPB3、HSPB5、HSPB6和HSPB8 db/db组明显低于db/m组(P<0.05);HSPB2、HSPB9和HSPB10 db/db组高于db/m组(P<0.05);而在db/db小鼠中LC3表达高于db/m组(P<0.01),而P62反之(P<0.01)。3)较db/m组,db/db组HSPB8、BAG3、LC3-Ⅱ蛋白表达均增高(P<0.01),相反P62蛋白表达减低(P<0.05)。结论1)10种sHSPs均在小鼠海马组织中表达,但表达特点有所不同。2)8周龄糖尿病小鼠海马组织中存在HSPB8蛋白表达增强,且自噬激活。

Objective To study the changes of small heat shock proteins(sHSPs)and autophagy-related proteins in hippocampus of spontaneous type 2 diabetic db/db mice.Methods The db/m mice were used as control group,while diabetic db/db mice were used as model group,10 mice in each group.The body weight,fasting blood glucose(FBG),the expression of small and medium heat shock protein family and autophagy-related genes in hippocampus were detected by real-time PCR,and the expression of HSPB8,BAG3,LC3 and P62 was detected by Western blot.Results 1)The body weight and fasting blood sugar of db/db mice were significantly higher than those of db/m mice(P<0.01).2)Small heat shock protein family B[small]member 1-10(HSPB1-10)gene was expressed in the hippocampus of mice.The expression of HSPB1,HSPB3,HSPB5,HSPB6 and HSPB8 in db/dbgroup was significantly lower than that in db/m group(P<0.05);the expression of HSPB2,HSPB9 and HSPB10 in db/db group was higher than that in db/m group(P<0.05);the expression of LC3 in db/db mice was higher than that in db/m group(P<0.01),whereas the expression of P62 was lower than that of db/m(P<0.01).3)The expression of HSPB8,BAG3 and LC3-Ⅱincreased in db/db group(P<0.01),but the expression of P62 decreased(P<0.05).Conclusions All sHSPs are expressed in the hippocampus of mice,but the expression profile is different.The expression of HSPB8 protein is increased and autophagy is activated in the hippocampus of 8-week-old diabetic mice.