脾切除术、脾动脉结扎术对肝硬化门脉高压大鼠血浆肿瘤坏死因子影响的实验研究

The effect on tumor necrosis factor in venous plasma of portal hypertension rat after splenectomy or splenic artery ligation

目的:研究肝硬化门脉高压症对大鼠血浆肿瘤坏死因子水平的影响;研究脾切除术、脾动脉结扎术对肝硬化门脉高压症大鼠血浆肿瘤坏死因子的影响;研究肝硬化门脉高压症血浆肿瘤坏死因子TNFα与一氧化氮合成酶NOS间的关系,探讨脾切除术后暴发性感染OPSI的可能机制。方法:健康大鼠被随机分为四组:正常对照组(10只)、实验对照组(10只)、脾切除组(30只)、脾动脉结扎组(30只)。后三组建成肝硬化门脉高压症动物模型。各组经实验处理后,放射免疫分析法动态(3天、7天、14天、)检测静脉血浆血肿瘤坏死因子水平;术后14天检测血浆一氧化氮合成酶NOS活性;观察术后4周内各组死亡率;行光病理学检查。在联想电脑上采用“SPSS for Windows”软件行数据统计学分析。结果:肝硬化门脉高压症大鼠血浆TNFα水平较正常对照组有明显增高(P<0.01);肝硬化门脉高压症脾切除组术后3天、7天、14天血浆TNFα水平与实验对照组相比较有显著性差异,脾动脉结扎组TNFα水平虽比实验对照组升高,但无显著性差异(P>0.05)。实验对照组血浆NOS活性明显高于正常对照组且血浆水平与NOS活性显著正相关(P<0.01,r=0.946);脾动脉结扎组NOS活性显著低于实验对照组及脾切除组(P<0.01)。脾动脉结扎组光镜观察发现脾实质轻度充血,少量散在出血灶。

Objective: In an attempt to study the effect of portal hypertension (PHT) on tumor necrosis factor (TNFα) in venous plasma, and the influence of splenectomy and splenic artery ligation on TNFα levels in venous plasma in PHT model rats; to investigate the relation between TNFα and NOS levels in venous plasma in PHT rats; and to explore the possible mechanism of overwhelming postsplenectomy infection (OPSI). Material and method: Healthy Wistar rats were randomized into four groups: normal control group (NCG n=10), model control group (MCG n=10), splenectomized group (SLC n=30), splenic artery ligation (SAL n=30). Later three groups were used to established PHT model. TNFα levels in venous plasma were dynamically measured by radioimmunoassay (RIA) at points (Day 3, Day 7, and Day 14) after the splenectomy and SAL; NOS levels in venous plasma were determined 14 days after operation. The mortality between SLC group and SAL group were compared 4 weeks after operation. Light microscope were applied to observed the pathological change. The statistical data were performed using the 揝PSS for Windows 8.0?on a legend computer. Results: PHT TNFα levels in venous plasma were significantly higher than NCG group (P<0.01). SLC group TNFα in plasma increased significantly, compared with MCG group (P<0.01), at points (Day 3, Day 7, and Day 14)after splenectomy. SAL group TNFα levels in venous plasma were slight higher than MCG group (P>0.05) but not significant, and were significantly lower than SLC group (P<0.01) at points (Day 3, Day 7, and Day 14) after SAL. MCG group NOS levels in venous plasma were significantly elevated (P<0.01), compared with NCG group, there was a positive correlation relationship (r=0.946, P<0.01) between TNFα level and NOS levels in venous plasma, while SAL group and SLC group respectively. Under the light microscope, slight congestion of spleen, a few sporadic hematoma and fibrosis of focal infarction, many fibres, norma ultrastructure of cells could be seen in SAL group 4 weeks after operation. At the same time, the morbidity of rate in SLC group was remarkably higher than SAL group (P<0.05). Conclusion: When PHT, TNFα levels in venous plasma significantly increase, possibly play a important role in the course of PHT. TNFα levels in venous plasma are significantly increase after splenectomy, while the morbidity rate also elevate remarkably. Compared with PHT model rats, SAL group TNFα levels and the morbidity rate are increased no significantly, and prognosis can be improved. These results indicate that TNFα which induces NOS after splenectomy may be one of the pathogenic mechanisms of OPSI.