血必净注射液对脓毒症大鼠基因调控的影响

Effect of Xuebijing injection(血必净注射液) on regulation of gene in rats with sepsis

目的:在基因水平探讨血必净注射液对脓毒症大鼠肝脏保护作用的机制。方法:采用盲肠结扎穿孔术(CLP)制备脓毒症模型。选择140只Wistar大鼠,其中60只随机均分为血必净治疗组和模型组,观察术后48 h和72 h的存活率;另80只按随机数字表法分为正常组、假手术组、模型组和血必净治疗组。透射电镜观察术后24 h肝脏病理学改变。采用含有4 096条大鼠基因cDNA克隆的表达谱基因芯片,检测并分析脓毒症大鼠经血必净注射液治疗后24 h肝组织的基因表达变化,并以计算机软件筛选出差异表达的基因。结果:与模型组比较,血必净治疗组大鼠48 h和72 h存活率显著升高,且血必净注射液有延长存活时间的作用(P<0.05或P<0.01)。24 h血必净治疗组肝脏病理学损伤改变明显减轻。在4 096条基因中,有差异表达的基因122条,下调基因主要涉及神经细胞与神经传导、细胞信号转导、各种基本生物化学物质代谢酶类基因、能量代谢相关基因;上调基因主要涉及细胞骨架与运动类蛋白、细胞周期调控、各种基本生物化学物质代谢酶类基因以及能量代谢相关基因。结论:血必净注射液能延长脓毒症大鼠的存活时间,并具有肝脏保护效应,其作用环节可能涉及物质代谢、脂类代谢基因、免疫、细胞信号转导等多方面。

Objective： To investigate the mechanism of Xuebijing injection （血必净注射液, XBJI） in protection of liver in rats with sepsis on gene level. Methods： According to cecum ligation perforation （CLP） method, the sepsis model was prepared. One hundred and forty Wistar rats were selected ;among them 60 rats were randomly divided into a model group and a XBJI treatment group, and the survival rates at postoperative 48 hours and 72 hours were observed ; the other 80 rats were randomly divided into 4 groups as follows ： sham operation group, normal control group, model group and XBJI treatment group to observe pathobiological changes of liver postoperative 24 hours through transmission electron microscope. After rat was treated by XBJI, adopted was expression spectra gene array which contains 4 096 rat gene cDNA, to detect and analyze the variation of gene expression of hepatic tissue in sieve genes that had differential expressions by means of rats with sepsis at postoperative 24 hours, and to a computer. Results： Compared with the model group, the survival rates of the rats in XBJI therapy group at 48 hours and 72 hours were notably raised （P（0.05 or P（0.01） . The liver pathobiological injury of XBJI therapy group obviously was relieved at 24 hours. There were 122 genes that had differential expressions out all of 4 096 genes. Down - regulation genes mainly referred to nerve cell and nerve conduction, cell signal transduction, various kinds of metabolic enzyme genes of basic biochemistry materials, energy metabolism related genes. Up -regulation genes mainly contained cytoskeleton and motion protein, cell cycle control, various kinds of metabolic enzymes genes of basic biochemistry materials, energy metabolism related genes. Conclusion： XBJI can obviously prolong the survival time of rat with sepsis and has a protective effect on liver, and the effect link may refer to substance metabolism, lipid metabolism gene, immunization, cell signal transduction and so on.