| Objective:To evaluate the effects of JGZ capsule on animal models of fatty liver,as well as the relationship between blood lipid and liver triglycerides, peroxisome proliferator activated receptors gamma (PPARγ) and low density lipoprotein receptor (LDLR) mRNA expression in hepatic cells of rats,study the effects of JGZ capsule on the fatty liver and explore the mechanism of molecular biology。it will be reported a new medicine of TCM and provided the research article of pharmacokinetics before clinic。Methods:1. Referring to literature prescription of high fat diet: feed 88% + lard 10.0% + cholesterol 1.5% +0.5% bile salt No.3, it was established animal models of fatty liver feeding with high fat diet[1]。Rats were randomized into 7 groups. Except the normal group, the other 6 groups of rats had been administered high fat diet for 3 months. At the same time, rats in JGZ capsule groups were given JGZ (7.5,15,30g/kg, p. o, daily) and rats in Dong-Bao-Gan-Tai group were administered Dong-Bao-Gan-Tai (1.5piece/kg, p.o, daily, 10 times as much as clinical adult dosage) and rats inSan-qi-zhi-gan-wan group were administered san-qi-zhi-gan-wan(2.5g/kg, p. o, daily, 10 times as much as clinical adult dosage)。2. Referring to literature,it was established animal models of fatty liver feeding with alcohol [2]: The rats in model groups were induced by ethanol intragastric infusion of 40%(v/v) ethanol orally 8 g/(kg·d),two times a day for the first 4weeks。Ethanol intragastric infusion of 50%(v/v) ethanol orally9g/(kg·d),two times a day for 2 monthes。Rats were randomized into 6 groups, Except the normal group, the other 5 groups of rats had been administered alcohol for 3 months。At the same time, rats in JGZ capsule groups were given JGZ (7.5,15,30g/kg, p. o, daily) and rats in Kai-Xi-Lai group were administered Kai-Xi-Lai (0.1g/kg,p.o,daily, 10 times as much as clinical adult dosage)。3. It were respectively measured that the contents of TP,ALB,ALT,AST,AKP,TG,TC,HDL-C,LDL-C,MDA,SOD,FFA,the blood viscosity and indexes in the serum and TG,TC,MDA,SOD,HL,LPL,FFA in the liver。The left leaf of liver was observed by histopathological staining,the immunohistochemical staining and RT-PCR were used to observe the effects on the expressions of PPARγmRNA and LDL-R mRNA。Result:1.The preventive effects of JGZ capsule on animal models of fatty liver 1.1 The effects of JGZ capsule on animal models of fatty liver with induced by high fat diet。compared with the normal group , the model group could remarkably increase the content of TP,ALB,ALT,AST,AKP,TC,TG,HDL-C,LDL-C,FFA,MDA,blood viscosity(Sr3) and assembling index of RBC in the serum (P<0.01),while remarkably decrease the content of SOD (P<0.01)。Compared with the model group , the low dose group of JGZ capsule could remarkably decrease the content of ALT,AST,TC(P<0.05);the middle dose group could remarkably decrease the content of TC,TG,FFA(P<0.05);the high dose group could remarkably decrease the content of ALT,AST,TG,FFA,MDA,blood viscosity(Sr3) and assembling index of RBC(P<0.05);the middle and high dose group could remarkably increase the content of SOD(P<0.05)。The result showed that JGZ capsule could remarkably decrease the content of ALT,AST,TC,TG,blood viscosity(Sr3) and assembling index of RBC and increase the content of SOD in the serum of the experimental fatty liver induced by high fat diet。Compared with the normal group , the model group could remarkably increase the content of TC,TG,FFA,MDA in the liver (P<0.01),while remarkably decrease the content of HL,LPL,SOD (P<0.01)。Compared with the model group,the middle dose group could remarkably decrease the content of TC,TG,FFA(P<0.05);the high dose group could remarkably decrease the content of TC,TG,FFA,MDA(P<0.01)。 At the same time,the middle dose group could remarkably increase the content of HL,LPL(P<0.05);the high dose group could remarkably increase the content of HL,LPL,SOD(P<0.01)。The result showed that JGZ capsule could remarkably decrease the content of TC,TG,FFA,MDA and increase the content of HL,LPL,SOD in the liver of the experimental fatty liver induced by high fat diet。1.2 The effects of JGZ capsule on animal models of fatty liver induced by alcohol。compared with the normal group , the model group could remarkably increase the content of ALT,TC,TG,FFA,MDAin the serum (P<0.01),while remarkably decrease the content of SOD (P<0.01)。Compared with the model group , the low dose group of JGZ capsule could remarkably decrease the content of ALT,AST,TG(P<0.01);the middle dose group could remarkably decrease the content of ALT,AST,TG,MDA(P<0.01);the high dose group could remarkably decrease the content of ALT,MDA(P<0.05);the middle and high dose group could remarkably increase the content of SOD(P<0.05)。The result showed that JGZ capsule could remarkably decrease the content of ALT,AST,TC,TG and increase the content of SOD in the serum of the experimental fatty liver induced by alcohol。Compared with the normal group , the model group could remarkably increase the content of TC,TG,FFA,MDA in the liver (P<0.01),while remarkably decrease the content of HL,LPL,SOD (P<0.01)。Compared with the model group,the middle dose group could remarkably decrease the content of TG,FFA(P<0.05);the high dose group could remarkably decrease the content of TC,TG(P<0.01)。At the same time,the high dose group could remarkably increase the content of HL,LPL(P<0.01);the high dose group could remarkably increase the content of HL,LPL,SOD(P<0.01)。The result showed that JGZ capsule could remarkably decrease the content of TC,TG,FFA and increase the content of HL,LPL,SOD in the liver of the experimental fatty liver with induced by alcohol。2.The effects of JGZ capsule on animal models of fatty liver to the pathomorphology of hepatic tissueThe observation of naked eye:the shape of liver was integrated,fresh red,capsule smooth and glossy in the normal group。The liver of the model group was soft,slicing greasy which volume and weight of increases,envelope strain,edge bluntness,there was significant difference compared with the normal group。JGZ capsule group have no significant difference in volume,weight,quality,color with the model group。The observation of microscope:The liver tissue in the normal group is complete and clear hepatic lobufe's construction is normal,the liver cell arranges orderly around the central vein,The same size and circle liver cell uncleus was clear,located the centre of polygonal cell,cytoplasm is abundant and afterbirth liquid is well-distributed。The hepatic construction disappears in the model group rat,hepatic lobule's boundary is not clear and arranges disorderly,mostly liver sinusoids disappears,There was many and different size lipid droplet vacuoles(fatty degeneration) in the expanded livers cell,as well as inflammatory cell intiltration and fibrosis increasing。JGZ capsule group was the similar the model group,but remarkably lighten inflammatory cell intiltration and fibrosis increasing, the high dose group was better than the other。3.The effects of JGZ capsule on animal models of fatty liver to the expression of PPARγand LDL-R mRNAThe RT-PCR and immunohistochemical staining results showed that,compared with the normal group,the model group could remarkably decrease the expression of PPARγand LDLR mRNA in the liver (P<0.01)。Compared with the model group,the middle and high dose group could remarkably increase the expression of PPARγand LDLR(P<0.05);the positive group could remarkably increase too(P<0.05)。The result showed that JGZ capsule could remarkably increase the expression of PPARγand LDLR mRNA in the liver of the experimental fatty liver。Conclusion:The results showed that JGZ capsule had good effects on the prevention of the experimental fatty liver, the possible action mechanism of JGZ capsule possess obvious effect of regulating the disorder of lipid metabolism, ameliorating hepatic function ,as well as anti-lipidperoxidation; the possible mechanism of molecular biology could obviously increase the expression of peroxisome proliferator activated receptors gamma (PPARγ) and low density lipoprotein receptor (LDLR) mRNA in hepatic cells of rats. |
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