| Objective:with the improvement of living standards, obesity and metabolic-related sy-ndrome has been spread rapidly around the world. Nonalcoholic fatty liver disease also has become one of the biggest threaten to the human healthy. The purpose of this resear-ch is to observe the effect of zhifanggantai capsule on NA-FLD and approach the latent mechanism of preventing it by a series of experiments. The zhifanggantai capsule is co-nsists of turmeric and giant knotwed with certain proportion. In addtion, in order to find out the more effective and safty drug to treat nonalcoholic fatty liver disease, pharmaco-dynamics of a comprehensive system of research is done for providing better guidance and comprehensive pharmacodynamics research materials for clinical medication and development of new drug to provide.Methods:1. Experimental sdudies of zhifanggantai capsule on nonalcoholic fatty liver by ethionine in mice:(1) 72 Km mouses, SPF,male and female half, the range of weight is 18 to 22 g,were randomly divided into 6 groups according to the weight and gender, including normal group, model group, ganlixing group and three zhifanggantai capsule groups (the primary drugs of each group are 0.89,1.78,3.56g/kg.BW), each group con-tains 12 mouses. Each of the dosage groups was administrated for 7 days with one day at a time, except the normal group and model group. After the last time,the other groups (except the normal group) was to give methionine at the dose of 250 mg/kg.BW. Then all groups were fasted for 24 hours but water, finally blood and tissue samples were col-lected for testing; (2) 80 Km mouses, SPF, male and female half, the range of weight is 18 to 22g, were randomly divided into 6 groups according to the weight and gender, in-cluding normal group,model group, ganlixing grow up and five zhifanggantai capsule groups(the primary drugs of each group are 0.44,0.89,1.78,3.56,7.12g/kg. BW), each group contains 12mouses. Each of the dosage groups was administrated for 7 days with one day at a time, except the normal group and model group. After the last time,the oth-er groups (except the normal group)was to give methionine at dose of 250 mg/kg.BW. Then all groups were fasted for 24 hours but water, finally blood and tissue samples we-re collected for testing;2. Experimental sdudies of zhifanggantai capsule on nonalcoholic fatty liver by hi-gh fat diet added with oxytetracycline in rat:Rats in the control group were fed with nor-mal food-stuffs (make up:0.2% sodium cholic acid+10% lard,10% egg yolk powder+ 1% cholesterol,1% standard feed) while those in the model group were fed with high fat food stuffs and injected with oxytetracycline every five days. The dose was 10mg/ 100g (per 1 ml ampoules containing 500mg drugs).The model group were divided into five groups, every group containing 12 rats, including model group, dongbaogantai gro-up and three zhifanggantai capsule groups(the primary drugs of each group are 0.74, 1.48,2.96g/kg), each group contains 12 rats after the model was developed successfully. They were administ-rated for four weeks successively, and the dose was 1ml/100 g with one day at a time.3. Experimental sdudies of zhifanggantai capsule on nonalcoholic fatty liver in ob/ ob mice:after adapting for 2 weeks,55 ob/ob mouses were randomly divided into 5 gr-oups according to the weights only six to eight weeks, including model group, dongbao-gantai group and three zhifanggantai capsule groups(the primary drugs of each group are 0.89,1.78,3.56 g/kg. BW),each group contains 11 mouses. Another wild type C57/ the BL6 mice was known as normal group with 11 mo-uses. All groups was administra-ted for six weeks, and the dose was O.lml/lOg with one day at a time. Results:1. Experimental sdudies of zhifanggantai capsule on nonalcoholic fatty liver by ethionine in mice:(1) compared with model group,the contents of TC, TG of liver tis-sue of zhifanggantai capsule (the primary drugs of each group are 0.89,1.78,3.56g/kg. BW)were decreased (p<0.01or p<0.05); zhifanggantai capsule (the primary drugs of ea-ch group are 1.78,3.56g/kg.BW) have the truned to lower serum content of TC and TG of liver but with no significant statistical difference (p>0.05); the liver coefficient and weight of zhifanggantai capsule(the primary drugs of each group are 0.89,1.78,3.56 g/ kg.BW) have no obvious change in (p>0.05); (2) compared with model group, the cont-ent of TG of the liver tissue of Zhifanggantai capsule(the primary drugs of each group are 3.56,7.12g/kg.BW) have turn lower (p<0.01 orp<0.05); Compared with model gro-up, the content of TC in liver tissue of zhifanggantai capsule (the primary drugs of each group are 0.89,1.78,3.56,1.78g/kg.BW)have turn lowe (p<0.05).2. Experimental sdudies of zhifanggantai capsule on nonalcoholic fatty liver by high fat diet added with oxytetracycline in rat:compared with model group, the content of TC, LDL-C of serum and TG of liver tissue of Zhifanggantai capsule (the primary d-rugs of each group are 0.74,1.48,2.96g/kg.BW)have reduced (p<0.01 or p< 0.05); zhi-fanggantai capsule (the primary drugs of each group are 1.48,2.96g/kg.BW) have made the level of MDA lower and SOD of liver tissue increase (p<0.05); Compared with mo-del group, zhifanggantai capsule(the primary drugs of each group are 2.96,1.48,0.74 g/ kg.BW) have no significant difference to TG, ALT, AST of serum and TC of liver tiss-ue,^ well as weight (p>0.05); The liver coefficient of Zhifanggantai capsule (the prim-ary drugs of each group are 0.74,1.48,2.96g/kg.BW) have decreased(p<0.01); the liver tissue structure of zhifanggantai capsule (the primary drugs of group is 0.74 g/kg.BW) arranges disorder,and it is easy to see scattered distribution of hepatocyte fatty degener-ation; the liver tissue structure of zhifanggantai capsule (the primary drugs of group is 1.48g/kg.BW)arranges slightly disorder, and it is a small am-ount of liver steatosis, as well as a local focal distribution; the liver tissue structure of Zhifanggantai capsule (the primary drugs of group is 2.96g/kg.BW)has roughly normal liver tissue structure, it can be found in a small amount of fatty degeneration.3. Experimental sdudies of zhifanggantai capsule on nonalcoholic fatty liver in ob/ Ob mice:Compared with model group,The content of LDL-C, MDA of serum and TG, MDA, TGF-b of liver tissue of zhifanggantai capsule (the primary drugs of each group are 0.89,1.78,3.56g/kg.BW) were decreased (p<0.01), respectly; the level of TC, TG, ALT and AST of zhifanggantai capsule(the primary drugs of each group are 0.89, 1.78,3.56g/kg.BW) are present a downward trend, and there are certain concentration response rela-tionship but with no significant statistical difference(p>0.05);the content of liver tissue INS of zhifanggantai capsule (the primary drugs of each group is 3.56 g g/kg.BW) has decreased (p<0.05); the level of ADP and TNF-a of liver tissue zhifang-gantai capsule (the primary drugs of each group are 1.78,3.56 g/kg.BW) have turned lower (p<0.05); compared with model group, the content of TC, FBG, SOD of liver tis-sue and liver coe-fficient of zhifanggantai capsule (the primary drugs of each group are 0.89,1.78,3.56g/kg.BW) have no obvious change, as well as weight(p>0.05); zhifang- gantai capsule (the primary drugs of each group is 0.89g/kg.BW) can be seen more big bubble steatosis in the liver tissue with diffusing in distribution, and its structure arran-ged disorder, cytoplasm osteoporosis is obvious; zhifanggantai capsule (the primary dr-ugs of each group is 1.78g/kg.BW)can be seen a small amount of liver steatosis, and str-ucture arranges slightly disorder in liver tissue; zhifanggantai capsule (the primary dru-gs of each group is 3.56g/kg.BW)can be seen a small number of large bubble steatosis in the liver tissue, and organizational structure is roughly normal.Conclusion:To investigate the effect of zhifanggantai capsule by the model of meth-ipnine on mice, NAFLD in rats and NAFLD in ob/ob mice.The influence of the experi-mental animal models of nonalcoholic fatty liver disease show better improvement of lipid metabolism,significantly reduce liver lipid levels,thus improving the structure of the liver tissue to lower the degree of pathological changes,reducing the high levels of the liver tissue MDA and SOD, improving the expression of liver tissue insulin. So as to further reduce the oxidative stress of liver cells of liver cell injury, and comprehensive results show that zhifanggantai caps-ule can better protect the liver cells. |
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