| Objective:Hepatic cirrhosis is the late stage of chronic liver diseases resulted from injury of hepatocytes and activation of the hepatic stellate cell (HSC) by several factors.Meanwhile, oxidative stress and several cytokines also play a role in the progress of the portal hypertension in cirrhosis. Portal hypertension is one of the main clinical manifestations in decompensation of cirrhosis and variceal bleeding as one complication of it threatens the patient life seriously.Heme oxygenase,as the original enzyme and rate-limiting enzyme of the metabolic pathway of heme,have three subtypes in total,of them HO-1 has the highest activity.HO-1 distributes all over the body and can be induced by several injuy factors which could result in oxidative stress on cells.HO-1 and its products,such as carbon monoxide,biliverdin and biliubin,have significant effects of anti-inflammation, anti-cell proliferation and regulation of the cytokines'expression.At present, octreotide is commonly used to treat variceal bleeding,but the mechanism of it on PH is unclear.This research aimed to make clear whether octreotide decreases PH by way of regulation of HO-CO system to investigat octreotide's potential mechanism of reducing PH and to vertify the effect of HO-CO system on PH,looking for the new therapy target for treatment of PH.Methods:Forty male SD rats were divided into three groups:8 in sham operated group (SH group),12 in portal hypertension group (PH group) and 20 in octreotide group (OCT group).The rat model with cirrhotic PH was established by common bile duct ligation in PH group and OCT group.OCT group was administrated octreotide intraperitoneally for 3 days after model establishment.PH group was treated with the same volume of saline. Then all rats were killed after measuring the portal venous pressure and the mean arterial pressure,in addition,blood and liver of them were taken out.Expression of HO-1 protein was observed by the immunohistochemical method. The level of HO-1 mRNA was observed by RT-PCR. Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) were assayed by automatic blood biochemistry analyzer.HE staining was performed to assess the proliferation and distribution of liver fibrosis tissue.Results:The rat model was reproduced successfullyThe rats in PH group were characterized by loose disarray, activity decrease, yellow urine, light stool, loss of appetite and abdominal distention.The level of serum ALT and AST in PH group(199.25±10.05,313.63±10.65) is higher than in SH(38.13±5.20 U/L,166.6±7.27 U/L) group (P＜0.01).HE staining shows that liver in PH group were characterized by pseudolobule, bile duct proliferation and a lot of inflammatory cells.The portal venous pressure in PH group (18.47±1.81 cmH2O) was higher than in SH group(9.13±0.62 cmH20) (P＜0.01).Octreotide influences the portal venous pressure and the mean arterial pressure in PH rat and protect the liverCompared to PH group, the portal venous pressure was lower (P<0.01) and the mean arterial pressure was similar in OCT group (P> 0.05).Octreotide has an effect on protecting the liver.Compared with PH group,the level of serum ALT and AST in OCT group was lower (P＜0.01).Compared with PH group,the proliferation of fibroblastic cells and infiltration of inflammatory cells in OCT group were decreased.The expression of HO-1 increased in the liver of rats with PH and octreotide could inhibit itImmunohistochemical method showed that the expression of HO-1 protein in PH group was significantly higher than in SH group and reducer than in OCT group(P< 0.01).RT-PCR showed that HO-1 mRNA expression in PH group was significantly higher than in SH group and reducer than in OCT group(P＜0.01).Conclusion:The expression of HO-1 was increased in cirrhotic rats with PH and octreotide could inhibit it. To regulate HO-CO system may be one of the effective mechanisms of octreotide on portal hypertension,revealing that HO-CO system played an important role on portal hypertension.
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