Role Of JAK2/STAT3Signaling Pathway In The Spleen Fibrosis Of Portal Hypertension Rats

Background:Splenomegaly is one of the most common complications of portal hypertension. Theincidence of splenomegalia is from36%to92%in cirrhosis. In China, splenomegalysecondary to portal hypertension always caused by hepatitis B related cirrhosis.Splenomegaly may lead to a series of complications:1, the oppression to surroundingorgans may result in corresponding symptoms;2, anemia due to hypersplenism;3, adecline in immune function;4, risk of splenic rupture under minor trauma;5, a decrease inthe blood volume. The proliferation of the fibrous tissue is one of the main causes andthe major pathological feature of splenomegalia in portal hypertension. The JAK2/STAT3signaling pathway which is known to mediate the signaling of numerous cytokines wasinitially found in cell differentiation. In follow-up studies, this pathway is found playingimportant roles in cell proliferation, apoptosis, immune function, and so on. Many studiesindicated that this pathway might participate in the development of fibrosis in certaintissues. An intense expression of the JAK2/STAT3signaling pathway in renal interstitialfibrosis demonstrates that it may be evolved in the development of tissue fibrosis. Other studies showed that the signaling pathway can induces the proliferation and the migrationof vascular smooth muscle cells. Collectively, these studies show that the JAK2/STAT3signaling pathway may play an important role in tissue fibrosis. However, whether thepathway contributes to the fibrosis of splenomegaly in portal hypertension is stillunknown.Objective:The expression of JAK2/STAT3signaling pathway in spleen of portal hypertensionwas studied, and the role of the pathway in process of fibrosis of splenomegaly in portalhypertension was analyzed. We hoped our results can give some new theory support totreat splenomegalia in portal hypertension.Method:Portal hypertension rats model was induced and randomly divided into the operatedgroup and AG490group, another group as sham-operated group was just received amidline abdominal incision. The fibrosis degrees of spleens were detected by Massontrichrome staining method. The expression of the P-STAT3protein was detected byimmunohistochemical method. The expression of the P-STAT3protein and the T-STAT3protein were detected by Western Blot.Result:1、The result of Masson trichrome staining showed that a considerable amount ofhyperplasia of fibrosis in the operation group compared to the AG490group, and thesham-operation group has the fewest amount of fibrosis. The difference was statisticallysignificant between the three groups (P<0.05).2、The results showed that cells with positive expression of P-STAT3protein weremainly positioned in areas of the spleen subcapsular, red pulp and marginal zone. Theexpression of P-STAT3protein in the operation group was significantly increasedcompared with the AG490group, and in the sham-operation group was least. Thedifference of P-STAT3protein between the three groups was statistically significant(P<0.05). The difference of T-STAT3protein between the three groups was notstatistically significant (P>0.05).3、Positively correlation was found between expression of the P-STAT3protein and was the degree of spleen fibrosis by Spearman correlation analysis (R=0.897, P<0.05).Conclusion:The P-STAT3protein is up-regulated in the spleen of portal hypertension rats, whichindicates that the activation of the JAK2/STAT3signaling pathway in portal hypertension.P-STAT3protein is related to the degree of spleen fibrosis, suggesting that JAK2/STAT3signaling pathway play an important role in the development of the spleen fibrosis ofportal hypertension.