芹黄素联合缺血后处理对大鼠肾缺血再灌注损伤的影响及机制探讨

发布时间：2019-01-20 11:21

【摘要】：目的探讨芹黄素联合缺血后处理(IPO)对大鼠肾缺血再灌注(I/R)损伤的影响及其机制。方法选择SD大鼠50只,分为假手术组(Sham组)、I/R组、I/R+芹黄素组、IPO组、芹黄素+IPO组各10只。I/R组、I/R+芹黄素组、IPO组、芹黄素+IPO组均制备肾I/R模型。其中,I/R+芹黄素组在制备I/R模型前经腹腔注射芹黄素10 mg/kg预处理;IPO组在阻断左肾动脉血流45 min后,给予反复3次的恢复血流10 s、阻断血流10 s的IPO处理,再完全恢复肾脏血流供应;芹黄素+IPO组在制备I/R模型前先予腹腔注射芹黄素10 mg/kg预处理,再给予IPO处理。Sham组仅分离肾包膜及肾动静脉而不阻断血流。各组干预24 h后,均经心脏取血测定血清BUN及Cr水平;取各组大鼠左肾组织,观察肾组织病理学变化;采用Real time PCR法检测肾组织高迁移率族蛋白1(HMGB1)、NF-κB、TNF-α和细胞间黏附分子1(ICAM-1)mRNA表达;采用Western blot法检测肾组织HMGB1蛋白表达。结果 I/R+芹黄素组、IPO组、芹黄素+IPO组血清BUN及Cr水平均低于I/R组(P均0.05);芹黄素+IPO组血清BUN及Cr水平均低于I/R+芹黄素组及IPO组(P均0.05)。病理检查示,Sham组未见明显的形态学改变;I/R组肾小管上皮细胞肿胀,部分细胞明显变性坏死;芹黄素+IPO组、I/R+芹黄素组和IPO组肾小管损伤程度明显减轻。I/R+芹黄素组、IPO组、芹黄素+IPO组HMGB1、NF-κB、TNF-α和ICAM-1 mRNA及蛋白表达均低于I/R组(P均0.05);芹黄素+IPO组HMGB1、NF-κB、TNF-α和ICAM-1 mRNA及蛋白表达均低于I/R+芹黄素组及IPO组(P均0.05)。结论芹黄素预处理联合IPO能够明显减轻肾脏I/R损伤,且其效果优于单一采用芹黄素预处理或IPO,其机制可能与抑制肾组织炎症反应有关。
[Abstract]:Objective to investigate the effects of celanthin combined with post-ischemic (IPO) on renal ischemia-reperfusion (I / R) injury in rats and its mechanism. Methods Fifty SD rats were divided into three groups: sham-operated group (Sham group), I / R group, IPO group and IPO group (n = 10). The renal I / R model was established in I / R group, I / R celanthin group, IPO group and celanthin IPO group. The I / R celanthin group was pretreated with celistein for 10 mg/kg before I / R model was established. In the IPO group, the left renal artery blood flow was blocked for 45 min, then the blood flow was restored for 10 s for 3 times, then the blood flow was blocked for 10 s, and then the renal blood flow was completely restored. The celanthin IPO group was pretreated with celistein for 10 mg/kg before I / R model was prepared, and then treated with IPO. In the Sham group, the renal capsule and renal arteriovenous were separated without blocking the blood flow. After 24 hours of intervention, the levels of serum BUN and Cr were measured by blood taken from the heart, and the pathological changes of renal tissue were observed by taking the left kidney tissue of the rats in each group. The expression of high mobility group protein 1 (HMGB1), NF- 魏 BnTNF- 伪 and intercellular adhesion molecule-1 (ICAM-1) mRNA in renal tissue was detected by Real time PCR assay and HMGB1 protein expression in renal tissue by Western blot method. Results the levels of serum BUN and Cr in I / R group, IPO group and IPO group were lower than those in I / R group (P 0.05), and the levels of BUN and Cr in IPO group were lower than those in I / R group and IPO group (P 0.05). Pathological examination showed that there were no obvious morphological changes in Sham group, tubule epithelial cells in I / R group were swollen, and some cells were obviously denatured and necrotized. The degree of renal tubule injury was alleviated in IPO group, I / R celanthin group and IPO group. HMGB1,NF- 魏 B in I / R celanthin group, IPO group and carvthin IPO group were significantly reduced. The expression of TNF- 伪, ICAM-1 mRNA and protein was lower than that of I / R group (P < 0. 05). The expression of HMGB1,NF- 魏 B TNF- 伪, ICAM-1 mRNA and protein in IPO group was lower than that in I / R group and IPO group (P 0.05). Conclusion the effects of celanthin preconditioning combined with IPO on renal I / R injury are better than those of IPO, alone. The mechanism may be related to the inhibition of renal inflammation.
【作者单位】：武汉大学人民医院;
【分类号】：R692

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