川芎素对大鼠肾脏缺血再灌注损伤的作用及其机制

ROLE OF SODIUM FERULATE IN ISCHEMIA-REPERFUSION INJURY IN RATS AND ITS MECHANISM

目的探讨川芎素对大鼠肾脏缺血再灌注损伤(I/R)保护作用及其机制。方法雄性SD大鼠随机分为假手术组、I/R组、川芎素组(10μmol/kg腹腔注射,LC组)、LC+Notch1通路激活剂rhNF-κB组(LC+rhNF-κB组),每组15只。观察各组血尿素氮(BUN)和血清肌酐(Scr)水平,采用实时定量PCR(qRT-PCR)和蛋白免疫印迹(Western blot)方法检测肾组织肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)的mRNA和蛋白表达水平,免疫组化和Western blot检测肾组织Caspase3、Bax/Bcl-2、Notch1、Jagged1的表达水平。结果 I/R组肾组织结构严重破坏,BUN、Scr、TNF-α、IL-6、Caspase3、Bax/Bcl-2、Notch1、Jagged1的表达均显著高于假手术组(P均<0.05),而LC组中上述蛋白的表达均显著低于I/R组(P均<0.05)。另外,LC+rhNF-κB组中BUN、Scr、TNF-α、IL-6、Caspase3、Bax/Bcl-2的表达与LC组相比均显著上调(P均<0.05)。结论川芎素通过抑制Notch1活化抑制肾组织的损伤和炎症反应。

Objective To investigate the protective effect of sodium ferulate against renal ischemia-reperfusion(I/R) injury in rats and its mechanism. Methods Male Sprague-Dawley rats were randomly divided into sham-operation group, I/R group, sodium ferulate group(10 μmol/kg by intraperitoneal injection), and sodium ferulate+Notch1 pathway activator rhNF-κB group(sodium ferulate+rhNF-κB group), with 15 rats in each group. The levels of blood urea nitrogen(BUN) and serum creatinine(Scr) were observed for each group;quantitative real-time PCR and Western blot were used to measure the mRNA and protein expression levels of tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) in renal tissue;immunohistochemistry and Western blot were used to measure the expression levels of Caspase3, Bax/Bcl-2, Notch1, and Jagged1 in renal tissue. ResultsCompared with the sham-operation group, the I/R group had severe structural damage of renal tissue and significantly higher expression levels of BUN, Scr, TNF-α, IL-6, Caspase3, Bax/Bcl-2, Notch1, and Jagged1(all P<0.05), and the sodium ferulate group had significantly lower expression levels of the above proteins than the I/R group(all P<0.05). In addition, compared with the sodium ferulate group, the sodium ferulate+rhNF-κB group had significantly upregulated expression levels of BUN, Scr, TNF-α, IL-6, Caspase3, and Bax/Bcl-2(all P<0.05). Conclusion Sodium ferulate inhibits renal tissue injury and inflammation by inhibiting the activation of Notch1.