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芹黃素聯(lián)合缺血后處理對(duì)大鼠腎缺血再灌注損傷的影響及機(jī)制探討

發(fā)布時(shí)間:2019-01-20 11:21
【摘要】:目的探討芹黃素聯(lián)合缺血后處理(IPO)對(duì)大鼠腎缺血再灌注(I/R)損傷的影響及其機(jī)制。方法選擇SD大鼠50只,分為假手術(shù)組(Sham組)、I/R組、I/R+芹黃素組、IPO組、芹黃素+IPO組各10只。I/R組、I/R+芹黃素組、IPO組、芹黃素+IPO組均制備腎I/R模型。其中,I/R+芹黃素組在制備I/R模型前經(jīng)腹腔注射芹黃素10 mg/kg預(yù)處理;IPO組在阻斷左腎動(dòng)脈血流45 min后,給予反復(fù)3次的恢復(fù)血流10 s、阻斷血流10 s的IPO處理,再完全恢復(fù)腎臟血流供應(yīng);芹黃素+IPO組在制備I/R模型前先予腹腔注射芹黃素10 mg/kg預(yù)處理,再給予IPO處理。Sham組僅分離腎包膜及腎動(dòng)靜脈而不阻斷血流。各組干預(yù)24 h后,均經(jīng)心臟取血測(cè)定血清BUN及Cr水平;取各組大鼠左腎組織,觀察腎組織病理學(xué)變化;采用Real time PCR法檢測(cè)腎組織高遷移率族蛋白1(HMGB1)、NF-κB、TNF-α和細(xì)胞間黏附分子1(ICAM-1)mRNA表達(dá);采用Western blot法檢測(cè)腎組織HMGB1蛋白表達(dá)。結(jié)果 I/R+芹黃素組、IPO組、芹黃素+IPO組血清BUN及Cr水平均低于I/R組(P均0.05);芹黃素+IPO組血清BUN及Cr水平均低于I/R+芹黃素組及IPO組(P均0.05)。病理檢查示,Sham組未見(jiàn)明顯的形態(tài)學(xué)改變;I/R組腎小管上皮細(xì)胞腫脹,部分細(xì)胞明顯變性壞死;芹黃素+IPO組、I/R+芹黃素組和IPO組腎小管損傷程度明顯減輕。I/R+芹黃素組、IPO組、芹黃素+IPO組HMGB1、NF-κB、TNF-α和ICAM-1 mRNA及蛋白表達(dá)均低于I/R組(P均0.05);芹黃素+IPO組HMGB1、NF-κB、TNF-α和ICAM-1 mRNA及蛋白表達(dá)均低于I/R+芹黃素組及IPO組(P均0.05)。結(jié)論芹黃素預(yù)處理聯(lián)合IPO能夠明顯減輕腎臟I/R損傷,且其效果優(yōu)于單一采用芹黃素預(yù)處理或IPO,其機(jī)制可能與抑制腎組織炎癥反應(yīng)有關(guān)。
[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- 偽 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- 偽, ICAM-1 mRNA and protein was lower than that of I / R group (P < 0. 05). The expression of HMGB1,NF- 魏 B TNF- 偽, 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.
【作者單位】: 武漢大學(xué)人民醫(yī)院;
【分類(lèi)號(hào)】:R692

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