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A Study on the Effects of Different Dose of Losartan in Rats with Portal Hypertension

Author: TianLingLin
Tutor: HuoLiJuan
School: Shanxi Medical
Course: Gastroenterology
Keywords: Cirrhosis Portal hypertension Losartan Hepatic venous pressure gradient Nitric oxide synthase
CLC: R575.2
Type: Master's thesis
Year: 2008
Downloads: 43
Quote: 0
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Abstract


Objective To investigate losartan (Losartan) with cirrhosis and portal hypertension (Portal hypertension, PHT) rat hepatic venous pressure gradient (HVPG) and its mechanism of action. The composite factor method rats cirrhosis PHT model will be the model for the formation of the surviving rats were randomly divided into model group and the three-dose treatment group, separate the normal control group. The treatment group were treated with different doses of losartan (10 mg.kg-1.d-1, 5 mg.kg-1.d-1 2.5mg.kg-1.d-1). After 21 days of treatment, the catheter measurement rats hepatic vein wedge pressure (WHVP) free hepatic venous pressure (FHVP) both get HVPG subtraction, and measurement of mean arterial pressure (MAP) and heart rate (HR ). Portal vein blood centrifuged to obtain serum, -20 ℃ storage, detect biochemical markers. The right lobe of the liver tissue to take part in 10% formalin solution fixed, HE and VG staining; another part of the production of liver homogenates, detection of nitric oxide (NO) and endothelial prime (ET). In addition, the use of immunohistochemical analysis of endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS) expression in the liver tissue. Results ① Compared with normal control group compared with the model group WHVP, HVPG was significantly higher (P lt; 0.05), FHVP., MAP and HR was no significant change; serum liver function indicators alanine aminotransferase enzyme (ALT), total bilirubin hormone (TBIL) significantly increased albumin (ALB) decreased (P lt; 0.05); liver fibrosis markers hyaluronic acid (HA) peptide and procollagen type Ⅲ (PC Ⅲ) was significantly higher (P lt; 0.05). Liver tissue collagen area increased significantly; reduced expression of liver tissue eNOS, iNOS expression increased significantly, while the liver sinusoidal volume significantly reduced; no significant change in the level of liver homogenates NO ET levels (P lt; 0.05). ② treatment 21 days after the end of the model control group compared with the HVPG of each treatment group were significantly lower (P lt; 0.05), for WHVP decline, but still higher than the normal control group, the differences between the three groups was not statistically significance. High dose group led MAP decreased significantly [from (94.44 ± 11.23) mmHg (70.81 ± 12.57) mmHg]. ③ compared with the model group, all treatment groups losartan can reduce the area of ??liver collagen, to reduce HA and ALT levels. ④ with the model group, eNOS expression in each treatment group was significantly higher (P lt; 0.05), the expression of iNOS and NO content in the liver increased ET levels decreased (P lt; 0.05), the hepatic sinusoid volume increases, the compare the difference between treatment groups was not statistically significant. Conclusion cirrhosis, liver sinusoidal volume decreased eNOS expression reduces liver sinusoidal endothelial cells, liver tissue iNOS expression increased intrahepatic NO / ET secretion disorders, is one of the reasons for increased intrahepatic resistance and portal vein pressure increased. The Losartan through regulation of eNOS and iNOS expression in the liver tissue, the intrahepatic NO generation increase ET levels, increased hepatic sinusoidal volume to some extent, restore the hepatic microcirculation hemodynamic also can alleviate liver fibrosis degree of play so as to reduce the role of HVPG reduce intrahepatic resistance. High dose losartan, while effectively reducing the HVPG, resulting in a decline in mean arterial pressure. In similar treatment with high-dose, low-dose, and systemic hemodynamics.

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CLC: > Medicine, health > Internal Medicine > Digestive and abdominal diseases > Liver and gall bladder disease > Cirrhosis
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