雷公藤内酯醇对大鼠肾缺血再灌注损伤时Toll样受体4表达的影响

Effects of Triptolide on expression of toll-like receptor 4 in renal ischemia-reperfusion injury

目的 观察雷公藤内酯醇（TRI）对大鼠肾缺血再灌注损伤时肾组织中Toll样受体4（TLR4）表达的影响.方法 随机将51只Wistar大鼠分为3组.（1）阴性对照组（n=15）：游离双侧肾脏,切除右肾,缝合腹壁.（2）缺血再灌注组（n=18）：实验过程与阴性对照组相同,但在切除右肾和游离左肾之后,将左肾动、静脉夹闭45 min,然后开通.（3）TRI处理组（n=18）：肾缺血再灌注前3 d经大鼠腹腔注射TRI 0.4 mg/kg,每天1次,连续3 d,其他实验过程与缺血再灌注组相同.肾缺血再灌注1、3、5 d后,分别采用全自动生化分析仪检测血清尿素氮（BUN）和肌酐（Cr）的含量;逆转录聚合酶链反应（RT-PCR）方法检测肾组织中TLR4 mRNA的表达水平;免疫印记法（Western blot）检测肾组织中TLR4表达水平.结果 肾缺血再灌注1、3、5 d后,缺血再灌注组和TRI处理组血清BUN及Cr均明显高于阴性对照组（P＜0.01）,肾组织中TLR4 mRNA和TLR4的表达也明显高于阴性对照组（P＜0.05）;但与缺血再灌注组比较,TRI处理组血清BUN和Cr明显降低（P＜0.01）,肾组织中TLR4 mRNA和TLR4的表达也显著降低（P＜0.05）.结论 雷公藤内酯醇可以减轻肾缺血再灌注损伤,其机制可能是通过抑制TLR4的表达而发挥作用的.

Objective To observe the effects of Triptolide on the expression of toll-like receptor 4 （TLR4） in renal ischemia/reperfusion （I/R） injury in rats. Methods A renal I/R model was established. Rats were randomly separated into the following experimental groups. Group 1, shamoperated control （n = 15） ： rats were subjected to surgical manipulation, without the induction of renal ischemia. Group 2, I/R （n = 18）： rats were subjected to left renal ischemia for 45 min followed by reperfusion. Group 3, TRI ＋ I/R （n = 18）： Before the I/R procedure （as in group 2）, rats were intraperitoneally injected with TRI （0.4 mg/kg）, once every day, three times. Rats were killed at the 1st, 3rd, and 5th day after I/R injury. The parameters of renal function were determined by autobiochemical analyzer. The expression of TLR4 was detected by RT-PCR and Western blotting. Results As comparedwith the sham-operated control group, serum BUN and Cr levels were significantly increased in the rats undergoing I/R procedure at the 1st, 3rd, and 5th day （P〈0. 01）. After the treatment with TRI, the levels of BUN and Cr and the expression of TLR4 in the renal tissues were significantly decreased （P〈0. 05）. Conclusion TRI could relieve renal I/R injury in rats by inhibiting the TLR4 expression.