姜黄素对大鼠脓毒症心肌损伤线粒体基因及高迁移率族蛋白B1的影响研究

Effect of curcumin on mitochondrial gene and high mobility group box 1 protein in sepsis myocardial injury of rats

目的观察姜黄素对大鼠脓毒症心肌线粒体相关基因(mtATP6)与高迁移率族蛋白B1(high mobility group box 1, HMGB1)mRNA表达及血浆HMGB1水平的影响,探讨脓毒症心肌损伤保护新策略。方法采用盲肠结扎穿孔术(cecal ligation and puncture, CLP)建立大鼠脓毒症模型。30只雄性SD大鼠随机(随机数字法)分成假手术组(Sham组)、脓毒症组(CLP组)、姜黄素干预组(Cur组),每组均为10只。Cur组大鼠造模后按100 mg/kg体质量予以腹腔注射姜黄素处理,Sham组及CLP组注射等量生理盐水。各组分别于建模后6 h、24 h随机(随机数字法)处死5只大鼠,光镜下观察大鼠心肌组织病理改变,检测血清中CK、CK-MB水平,采用ELISA法检测血浆中HMGB1水平,Real-time PCR检测心肌组织中HMGB1 mRNA及mtATP6的表达。三组间均数比较采用单因素方差分析,组间两两比较采用LSD-t检验,以P<0.05为差异有统计学意义。结果Cur组心肌组织病理评分在6 h、24h低于CLP组(P<0.05);Cur组CK及CK-MB在6 h、24 h均低于CLP组(P<0.05);Cur组血浆HMGB1水平在6 h、24 h均低于CLP组(P<0.05);CLP组大鼠心肌组织中HMGB1 mRNA及mtATP6表达水平在6 h均低于Sham组(P<0.05),而Cur组大鼠心肌组织中HMGB1 mRNA及mtATP6表达水平在6 h均高于CLP组,但差异无统计学意义(P>0.05)。结论姜黄素通过影响HMGB1释放及移位下调胞外水平、调控mtATP6的表达水平,对CLP造模大鼠急性心肌损伤具有保护作用。

Objective To observe the effect of curcumin on myocardial mitochondrial related gene (mtATP6), high mobility group box 1(HMGB1) mRNA expression and plasma HMGB1 level in rats with sepsis, and to explore a new strategy for protection of myocardial injury in sepsis. Methods A rat sepsis model was established by cecal ligation and puncture (CLP). Thirty male Sprague-Dawley rats were randomly (random number) divided into the sham operation group (sham group), sepsis group (CLP group), and curcumin intervention group (Cur group), with 10 rats in each group. Rats in the Cur group were treated with curcumin by intraperitoneal injection at 100 mg/kg, and normal saline was injected into rats in the sham and CLP groups. Five rats were randomly (random number) sacrificed at 6 h and 24 h after modeling. The pathological changes of myocardial tissue were observed under light microscope. The levels of CK and CK-MB in serum were detected. The HMGB1 level in plasma was detected by ELISA. Real-time PCR was used to detect the expression of HMGB1 mRNA and mtATP6 in myocardial tissue. One-way ANOVA were performed in multigroup mean comparison, LSD-t test was used to compare the mean values of two samples, and P<0.05 was considered statistically significant. Results The pathological score of myocardial tissue in the Cur group was lower than those in the CLP group at 6 h and 24 h (P<0.05). The CK and CK-MB in the Cur group were lower than those in the CLP group at 6 h and 24 h (P<0.05). The levels of HMGB1 in the Cur group were lower than those in the CLP group at 6 h and 24 h (P<0.05). The expression levels of HMGB1 mRNA and mtATP6 in myocardial tissue of the CLP group were lower than those in the sham group at 6 h (P<0.05), while the expression levels of HMGB1 mRNA and mtATP6 in myocardial tissue of the Cur group were higher than those in the CLP group at 6 h, but the difference was not statistically significant (P>0.05). Conclusion Curcumin protects acute myocardial injury by affecting HMGB1 release and translocation down-regulation of extracellular levels and regulation of mtATP6 expression in CLP model rats.