الفهرس 
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Abstract
Liver fibrosis represents a major worldwide health care burden. It is the outcome of many chronic liver diseases, including hepatitis B virus (HBV), hepatitis C virus (HCV), alcoholic liver disease, and nonalcoholic steatohepatitis (NASH), liver intoxication (drug or nutritionally related). It is manifested by massive accumulation of the extracellular matrix (ECM) and scar formation. Several injury triggering events play a critical role in the pathogenesis of liver fibrosis. Currently, effective therapy for hepatic fibrogenesis exists for several diseases in which the cause of the underlying disease is removed. In contrast, specific therapy directed only at the fibrotic lesion is not currently available; the most effective therapies will most likely be directed at the stellate cell. So we aimed in this study to explain the therapeutic effect of exogenous interleukin-10 on reversing well-established hepatic fibrosis after 9 weeks of CCL4 administration on experimental rats.
108 adult male albino rats used in this study weighing about 180-280 g, were divided into 4 groups, each group contains 27 rats. The first group was reserved as control. In the second group rats were injected subcutaneously with 0.2 mL/100 g of CCl4 twice a week for nine weeks for induction of hepatic fibrosis then put to death. In the third group rats were left for spontaneous recovery for three weeks after induction of fibrosis by CCl4 and then put to death. In the fourth group rats were treated with IL-10 (4 ug/kg) subcutaneously three times a week for three weeks after induction of fibrosis by CCl4 and then put to death.
Liver sections from all above groups were kept for histological techniques to be stained with H&E and Masson’s trichrome stains. Other sections were taken and kept for immunohistochemistry technique, to detect α-SMA expression in the liver tissue in all above groups.
Samples of rat serum were kept for measurement of biochemical parameters (ALT, AST and albumin) and the level of the TGF-β1 ELISA kit.
The histological activity index (HAI) of rats in the present study, was assessed for both the degree of inflammation and the stage of fibrosis.
Regarding, grading of inflammation: It was observed that there was no inflammation in control group. In contrast there was marked inflammation (grade 3) in CCl4-induced fibrosis group and moderate inflammation (grade 2) in spontaneous recovery group. Meanwhile the administration of IL-10 in group D resulted in marked decreasing of the grading of inflammation (grade 1) compared to CCl4-induced fibrosis group.
On staging of fibrosis: It was observed that there was no fibrosis in control group. In contrast there was a marked fibrosis reaching to cirrhosis (stages 3 &4) in CCl4-induced fibrosis group. The degree of fibrosis showed mild decreased (stage 3) in spontaneous recovery group. Meanwhile the administration of IL-10 in group D resulted in marked decrease in the stage of fibrosis to (stage 1).
In the present study, the biochemical parameters were measured to verify the role of IL-10 in the protection of the liver from injury. ALT, AST and albumin were within normal levels in control group. These parameters were dramatically increased in CCl4-induced fibrosis group. Also, these parameters were increased in spontaneous recovery group but less than the levels of CCl4-induced fibrosis group. The activities of serum ALT and AST and albumin were significantly reduced by administration of IL-10 nearly close to the normal levels compared to control group.
Serum TGF-β1 concentration was measured by ELISA. The concentration was dramatically increased in CCl4-induced fibrosis group compared to the control group. The level of TGF- β 1 in serum was increased in spontaneous recovery group but less than the levels of CCl4-induced fibrosis group and was significantly reduced in the IL-10 treated group.
Immunostaining of α-SMA expression in liver sections shows the following changes:
No α-SMA expression in the control group.
In the second group (CCl4-induced fibrosis group), there was marked cytoplasmic expression for α-SMA on indicating marked fibrosis. In the third group (spontaneous recovery group), there was moderate expression of α-SMA. While in the fourth group (IL-10treated group), there was mild expression of α-SMA indicating marked improvement of fibrosis.