The Therapeutic Effects And The Mechanisms Of Rhubarb On Intrahepatic Cholestasis In Infantile Rats

【Objective】Base on the animal model, the aims of this study are of making clear that: (1) the therapeutic effects of rhubarb on intrahepatic cholestasis in rats (2) the mechanisms of rhubarb treatment on the cholestatic infantile hepatitis syndrome (3) the theoretical evidence on the rhubarb treatment of intrahepatic cholestasis. 【Methods】 (1) Jaundice model with intrahepatic cholestasis was established in infantile rats induced by the ANIT ( α -Naphthyl isothiocyanate , ANIT). Dosage used in the animal model establishment of ANIT was 60mg/kg. (2) Animals were divided into five groups according to the treatment: therapeutic group with rhubarb, control group without any treatment; therapeutic control group 1 with UDCA (Ursodeoxychlic Acid, UDCA), therapeutic control group 2 with UDCA and deltasone, mock group without ANIT and treatment. (3) At the time of the second week, the third week, and the forth week, (a) the serum concentration of TB, DB, ALT, ALP and TBA were assessed by automatic biochemical analyzer (b) the concentrations of NO (Nitric Dxide, NO), MDA (Maleic Dialdehyde, MDA) and T-AOC (The ability of total antioxidation, T-AOC) in liver were measured in the homogenate of liver tissue (c) the histological changes of liver were observed respectively by light microscope and electronic microscope respectively. 【Results】 (1) Compare with the mock group, serum concentrations of TB and DB were increased in the controlled untreated group. Further studies showed that the ratios of DB to TB were more than 50% on each of time point (the second week: 60.92±32.38/117.66±28.70; the third week: 68.80±2.82/133.94±8.78;the fourth week: 77.80±5.64/154.70±0.52). These results indicated that the hyperbilirubinemia induced by the ANIT was predominantly caused by the increasing of DB. And there were significant differences in serum concentrations of ALT, ALP and TBA between the controlled untreated group and the mock group(P﹤ 0.01). The animal model of hepatic jaundice with cholestasis was successfully established. (2) Compare with the controlled untreated group, the serum concentrations of DB, TB, ALP, ALT and TBA were significant lower in the therapeutic group with rhubarb (P<0.05). Meanwhile, better effects can be observed on relieving the jaundice and decreasing the ALP, TBA level with rhubarb treatment than the UDCA group or combination with UDCA and deltasone treatment group. (3) T-AOC in liver tissue in untreated group was much lower than that of in the mock group, while NO and MDA were much higher than those in the mock group. But after the rhubarb treatment, T-AOC in liver tissue was increased and became much higher than that of in the untreated group. While the NO and MDA get lower than those in theuntreated group. (4) In the group of untreated rats, much bilirubin crystal can be observed in the biliary canaliculi and hepatocytes. Remarkably cloudy swelling, ballooning-like degeneration of hepotocytes with fibrosis in portal area can be found in livers by light microscope; while only mild change can be seen in rhubarb treated group. Expansion of cholangiole, destroying of tight junction between hepatic cells, swelling of mitochondrion, hyperplasia of collagen fibers can be found in the untreated group via electron microscopy, while in the rhubarb treated group, only mild swelling of mitochondrion as well as focal kytoplasm solution of liver cells can be observed. No cholangiole expansion can be observed in the rhubarb treated group. 【Conclusions】 (1) Infantile rat model of cholestatic jaundice can be induced by the ANIT. The pathophysiological changes of this rat model are the same as the most of the infantile cholestatic hepatic syndrome in human. (2) Rhubarb is an effective drug in treating the intrahepatic cholestasis. Not only can it remarkably reduce the serum concentration of TB, DB, ALT, ALP and TBA, but also relieve the toxicity of bile acid and inhibit the hepatic injury or fibrosis. (3) The treatment effects of rhubarb on the intrahepatic cholestasis may caused by decreasing the level of...