脾动脉缩窄对门静脉高压大鼠脾脏iNOS表达及Th1/Th2平衡的影响

摘要

目的 观察脾动脉缩窄对肝硬化门静脉高压大鼠脾脏iNOS、Th1/Th2型细胞因子表达的影响,并探讨机制.方法 肝硬化门静脉高压大鼠随机分3组(n=10):假手术组(SOG)、脾动脉缩窄术组(SAC)和脾动脉结扎术组(SAL);正常大鼠10只行假手术作为对照组(NCG).免疫组化法测脾脏iNOS表达,RT-PCR法测脾脏IFN-γ、IL-4mRNA表达,对iNOS与IFN-γ、IL-4表达量作相关分析.结果 SOG脾脏iNOS明显高于NCG(P＜0.01),SAC和SAL明显低于SOG(P＜0.01).SOG脾脏IFN-γmRNA和IFN-γ/IL-4明显低于NCG(P＜0.01),IL-4mRNA明显高于NCG(P＜0.01);SAC脾脏IFN-γmRNA高于SOG(P＜0.05),SAC和SAL脾脏IL-4mRNA低于SOG(P＜0.05),而IFN-γ/IL-4高于SOG(P＜0.05).iNOS与IFN-γ负相关(r=-0.672,P＜0.01),与IL-4正相关(r=0.634,P＜0.01).结论 脾动脉缩窄术后门静脉高压大鼠脾脏iNOS表达降低,IFN-γ/IL-4升高,脾脏Th1/Th2失衡改善可能与术后iNOS表达降低有关.%Objective To investigate the effect and the potential mechanism of splenic artery coarctation on the expression of iNOS and Th1/Th2 cytokines in spleen of cirrhotic rats with portal hypertension (PHT). Methods Cirrhotic rats were randomized into 3 groups (n= 10):sham operation group (SOG), splenic artery coarctation group (SAC) and splenic artery ligation group (SAL). Ten normal rats treated with sham operation were employed to serve as normal control group (NCG). Immunohistochemial staining was used to observe iNOS. RT-PCR was used to detect IFN-γ and IL-4mRNA. The Pearson's correlation analysis was used to investigate the relationship between iNOS and IFN-γ or IL-4. Results The expression of iNOS was increased significantly in spleen of cirrhotic rats as compared with NCG(P＜0. 01). It was decreased after SAC and SAL compared with SOG (P＜0. 01). The expression of IFN-γmRNA and IFN-γ/IL-4 of SOG were decreased but IL-4mRNA increased significantly than that of NCG(P＜0.01). IFN-γmRNA was increased after SAC compared with SOG (P＜0.05). IL-4mRNA was decreased and IFN-γ/IL-4 increased after SAC and SAL compared with SOG (P＜0. 05). The expression of iNOS was negatively correlated with the expression of IFN-γmRNA(r=-0.672, P＜ 0.01 ) and positively correlated with the expression of IL-4 mRNA (r=0.634,P＜0. 01). Conclusion The expression of iNOS is decreased and IFN-γ/IL-4 increased after SAC in spleen of cirrhotic rats with PHT and it may improve Th1/Th2 polarization by reducing the expression of iNOS.