依那西普靶向治疗影响2型糖尿病大鼠肾脏TRAIL系统表达的观察

Effects of targeted etanercept therapy on the expression of tumor necrosis factor-related apoptosis-inducing ligand system in kidney of type 2 diabetic rats

目的观察依那西普靶点治疗对T2DM大鼠肾组织肿瘤坏死因子相关的凋亡诱导配体(TRAIL)系统表达的影响,探讨其肾脏保护作用机制。方法建立T2DM大鼠模型。成模后将大鼠随机分为4组:正常对照(NC)组、模型对照(T2DM)组、阿托伐他汀治疗(DA)组、依那西普治疗(DE)组。用ELISA、免疫组化、Q-RT-PCR法等分别检测尿α1-微球蛋白(Uα1-MG)、血清TNF-α,及TNF-α、TRAIL、死亡受体4(DR4)、诱骗受体2(DcR2)在肾组织表达。结果与NC组比,各时间点DM组大鼠Uα1-MG、血清TNF-α显著升高(P<0.01),肾组织TNF-α、DcR2表达显著增强(P<0.01);而TRAIL、DR4表达(P<0.01)显著减弱。治疗后各指标均呈相反改变。与DA组比较,DE组大鼠Uα1-MG、血清TNF-α降低更显著(P<0.01)。与DE组比较,治疗后DA组大鼠肾组织TNF-α、TRAIL、DR4表达增强(P<0.01,P<0.05),DcR2表达减弱(P<0.01)。结论靶点治疗通过影响TNF-α及TRAIL系统的表达,对T2DM大鼠具有显著的肾脏保护作用。

Objective To explore the effect of targeted etanercept therapy on the expression of tumor necrosis factor-related apoptosis-inducing ligand system （TRAIL） in the kidneys of type 2 diabetes rats. Methods The rat models of type 2 diabetes were randomly divided into diabetic model group （DM）, atorvastatin treatment group （DA） and etanercept treatment group （DE）, with the control rats fed with normα1 chow （NC）. After treatment, the levels of serum TNF-α and urine α1-MG （Uα1-MG） were detected by ELISA, and the protein and rnRNA expressions of TNF-α, TRAIL, death receptor 4 （DR4） and decoy receptor 2（DcR2） in the kidney were measured by immune histochemistry and quantitative reα1- time PCR （Q-RT-PCR）. Results Compared with NC group ,the levels of Uα1-MG, serum TNF-α,and the renα1 expressions of TNF-α and DcR2 protein and mRNA increased significantly （P〈0. 01） ;however, the expressions of TRAIL and DR4 protein and mRNA （P〈0. 01）reduced significantly in the DM group. These abnormα1 changes were α1l significantly reversed after treatment with etanercept and atorvastatin. Treatment with etanercept resulted in a rapid and more obvious reduction of Uα1-MG and serum TNF-α as compared with atorvastatin treatment （P〈0. 01）. The increments of renα1 protein and mRNA expressions of TNF-α, TRAIL, and DR4 （P〈 0. 01, P〈0. 05）, and the reduction of renα1 protein and mRNA expressions of DcR2 （P〈0. 01）were more obvious in DA group than in DE group. Conelusima Targeted treatment with etanercept for T2DM rats has significant renα1 protections, its mechanisms may be theeffects of etanercept on expression of TNF-α and the TRAIL system.