水飞蓟宾-磷脂酰胆碱复合物对脓毒症大鼠脑保护作用

摘要

Objective In order to search for a new technique for the clinial treatmeant of sepsis, this study investigate the effect and explore the mechanism of silybin - phosphatidylcholine compound (SPC) on sepsis induced acute injury rats by detecting the changes of MDA, SOD, TNF -a, IL -6. Methods Sepsis model were made by cecal ligation and puncture ( CLP) , but sham operation control group(10 rats)had no CLP,with only nip few times on the end of appendix. The high dose of SPC group and the low dose of SPC group were treated with SPC 200mg/kg and lOOmg/kg respectively 1 hour before established models. The rats in both groups were treated with SPC 200mg/kg and lOOmg/kg 1 hour after CLP operation. The level of TNF - a, IL - 6 were measured by double antibody enzyme -linked immune sorbent assay( ELISA) experimentation. The level of SOD and MDA in brain tissues were measured by xanthine oxidase (XO)method and thibatituric acid (TBA) method. Results The CLP rats' brain tissues MDA level was significantly elevated compared to the control group (P<0.01) ,but SOD level was striking reduced in brain tissues compared to the control group (P<0.01). Low and high dose SPC had significant effect on the changes of level of MDA and SOD (P < 0. 05 ). The level of serum TNF - a and IL - 6 was significantly increased compared to the control group (P < 0. 01). Low dose and high dose SPC can obviously depress the serum phlegma-sia medium level in CLP rats compared to the control group (P <0.05). Histopathological microscope observed that in the sepsis group neuron loss was decreased and both normal and dead cells existed. Conclusion SPC possesses potential protective effect on sepsis - induced hepatic and cerebullar injury in rats by inhibitting inflammation factors and decreasing free radical which leades to secondary lesion to hepatic and brain.%目的 本研究通过使用水飞蓟宾-磷脂酰胆碱复合物(silybin-phosphatidylcholine compound,SPC)对脓毒症大鼠进行预防和治疗,通过检测脑组织中丙二醛(MDA)、超氧化物歧化酶(SOD)的活性,肿瘤坏死因子(TNF-α)、白介素-6(IL-6)水平的变化,观察SPC对脓毒症大鼠脑损伤的影响,并探讨其作用机制,为临床治疗脓毒症所致脑损伤提供新的思路和方法.方法 采用盲肠结扎穿孔术(cecal ligation and puncture,CLP)致脓毒症模型,伪手术对照组只打开腹腔,在盲端处捏几下,不结扎也不穿孔.SPC高、低剂量组分别于造模前lh灌胃,手术后lh再灌胃给予同样剂量的SPC,造模方法同模型组.采用双抗体夹心酶联免疫吸附法检测血中TNF-α及IL-6,观察各组TNF-α、IL-6含量变化,采用黄嘌呤氧化酶法和硫代巴比妥酸法测定脑组织SOD及MDA的水平变化.结果 造模后大鼠脑组织中MDA值明显升高,SOD活性明显下降,血清中TNF-α、IL-6含量明显升高,与伪手术组比较,差异明显(P＜0.01),高、低剂量的SPC对脑组织中MDA、SOD的变化均有明显的影响,可明显降低脓毒症大鼠血清中的炎性介质水平,与模型组相比有显著差异(P＜0.05).组织学光镜观察SPC组与模型组相比较神经元脱失减少,正常与坏死细胞相间存在.结论 SPC可能通过抑制和减少自由基的生成,抑制和对抗炎症因子来减少脓毒血症各种有害因子对脑组织的继发性损害,从而达到保护脑组织的作用.