JAK2/STAT3信号通路在门静脉高压大鼠模型脾脏纤维化过程中的作用

Effect of JAK2/ STAT3 Signaling Pathway in the Spleen Fibrosis of Portal Hypertension

目的:探讨Janus蛋白酪氨酸激酶2/信号转导子和转录激活子3(JAK2/STAT3)信号通路在门静脉高压大鼠模型脾脏纤维化过程中的表达和作用。方法:采用缩窄门静脉的方法制备门静脉高压大鼠模型,通过给予JAK2特异性抑制剂AG490阻断JAK2/STAT3信号通路。30只SD(Sprague Dawley)大鼠随机分为单纯手术组、AG490组、假手术组(n=10)。AG490组每天给予5 mg/kg体重的AG490,另外两组每天给予相同体积的生理盐水,连续2周后处死大鼠,计算各组脾指数,Masson三色染色检测脾脏组织纤维化程度,免疫组织化学和Western blotting检测脾脏组织中磷酸化STAT3(p-STAT3)蛋白的表达水平。结果:单纯手术组p-STAT3蛋白水平较假手术组明显升高(P<0.05),AG490组较单纯手术组明显降低(P<0.05);单纯手术组脾指数、脾脏纤维化程度较假手术组明显升高(P<0.05),AG490组较单纯手术组明显降低(P<0.05);p-STAT3蛋白水平与脾脏纤维化程度呈明显的正相关趋势(r=0.897,P<0.05)。结论:JAK2/STAT3信号通路与门静脉高压大鼠脾脏纤维化过程关系密切,阻断该通路可以减轻门静脉高压脾脏纤维化的程度。

Objective： To investigate the effect of JAK2/STAT3 signaling pathway on the spleen fibrosis of portal hypertension rats. Methods： Portal hypertension rat model was induced by partial portal vein ligation （PVL） and the specifically inhibitor, AG490 was used to block the JAK2/STAT3 pathway. 30 SD rats were randomly divided into three groups, the group of PVL, the group of PVL treated with AG490 and the group of sham-operation （n=l 0）. The group of PVL treated with AG490 were treated with daily injection of a specific JAK2 inhibitor AG490 until sacrifice while the group of PVL and the group of sham-operated were treated with daily injection of the same volume of saline water. Rats were sacrificed at 14 days later. Spleen index were measured and interstitial fibrosis were assessed by Masson trichrome staining. Immunohistochemistry and western blot were used to detect the expression of the phosphorylation of STAT3. Results： JAK2/STAT3 signaling transduction pathway was activated in the spleen of portal hypertension mrs model. The activation of JAK2/STAT3 was closely correlated＇with the progression of the spleen fibrosis （ correlation coefficient = 0.897, P 〈 0.01, Spearman P test）. AG490 treatment significantly reduced the spleen fibrosis [（10.19~ 1.19）% VS（19.85% 1.58）%, P〈0.05]. Conclusion： JAK2/STAT3 signaling pathway plays an important role in fibrosis process of spleen associated to the portal hypertension.