| Objective:To observe the safety and effect of Xiao Zhi Tang, atorvastatin and metformin treatment on a high fatdiet induced mice model of hyperlipidemia, obesity and nonalcoholic fatty liver, and their effect on metabolism of vitamin D3.Methods:In the preliminary study, Wister rats were fed with a2-week high fat diet to induce hyperlipidemia and nonalcoholic fatty liver. Then the rats were randomly assigned into model group, high-dose Xiao Zhi Tang treatment group, middle-dose Xiao Zhi Tang treatment group, low-dose Xiao Zhi Tang treatment group, and atorvastatin treatment group, and fed with the high fat diet for another30days. The rats in the control group were given normal diet throughout the preliminary study. Blood and liver samples were collected at the endpoint for analysis. Given the result of the preliminary study, middle-dose Xiao Zhi Tang was selected for the final study. In the final study, male Ldlr-/-mice on a genetic background of C57BL/6J were fed with a high fat/high cholesterol diet for10weeks and became hyperlipidemicand obese. Then the Ldlr-/-mice were assigned randomly into the model group, metformin treatment group, atorvastatin treatment group and (middle-dose) Xiao Zhi Tang treatment group (8mice in each group) and fed with the high-fat/high cholesterol diet for another10weeks. In treatment groups, metformin, atorvastatin and Xiao Zhi Tang were given to the Ldlr-/-mice respectively. A control group with8C57BL/6J mice received no treatment and was fed with a normal diet throughout the study. At the endpoint of the study, blood and organ samples of all mice were collected for analysis.Result:1) A2-week high fat diet successfully induced hyperlipidemia in Wister rats in the preliminary study. After a treatment duration of30days, high-dose and middle-dose Xiao Zhi Tang as well as atorvastatin significantly decreased the TC, LDL-TC level (P＜0.01). The high-dose and middle-dose Xiao Zhi Tang slightly raised the HDL-TC level (P>0.05). The morphological finding showed a successful model of nonalcoholic fatty liver in model group and improvement in middle-dose Xiao Zhi Tang treatment group.2) A mice model of hyperlipidemia, obesity and nonalcoholic fatty liver was successfully induced in Ldlr-/-mice by a high fat/high cholesterol diet.3) After fed with the high fat/high cholesterol diet for10weeks, TC (P<0.01) and TG (P<0.05) level were significantly higher in model group Ldlr-/-mice than the C57BL/6J mice in the control group. At the endpoint of the final study, the model group Ldlr-/-mice had higher insulin and leptin level(P<0.05), and higher HOMA-IR and HOMA-β (P＜0.05) than the C57BL/6J mice in the control group. Meanwhile, the model group Ldlr-/-mice had lower insulin and leptinlevel(P<0.05) in liver tissue. The oil red O staining found severe to very severe hepatic steatosis, as well as many big lipid-droplet fractions.4)(middle-dose) Xiao Zhi Tang significantly decreased the TG (P＜0.05), serum insulin, serum leptin, and HOMA-IR level (P＜0.01), and significantly increased the serum GLP-1level (P＜0.05), and insulin and leptin level in liver tissue (P＜0.01). Lipid-droplet fractions in level tissue were smaller in (middle-dose) Xiao Zhi Tang treatment group as well.5)Atorvastatin significantly decreased the TG (P＜0.05), higher serum insulin (P＜0.05), serum leptin(P<0.05), and HOMA-IR level (P＜0.01), significantly increased the serum GLP-1level (P＜0.05), slightly decreased the insulin and leptin level in liver tissue (P>0.05), and significantly decreased the IL-6level in liver tissue (P<0.05). Lipid-droplet fractions in level tissue were smaller in atorvastatin treatment group as well.6) Metformin did not significantly changed the TC, TG, serum insulin, serum leptin, HOMA-IRand HOMA-0level (P>0.05). Metformin significantly increased the insulin level in liver tissue and the serum AST, while significantly decreased the VDR level in ileumtissue(P<0.05).Lipid-droplet fractions in level tissue were smaller in metformin treatment group, yet the severity of hepatic steatosis was the same with that of the model group.Conclusion:1)A2-week high fat diet could successfully induce hyperiipidemia in Wister rats.2) A mice model of hyperlipidemia, obesity.nonalcoholic fatty liver, insulin resistance, and leptin resistance could be successfully induced in Ldlr-/-mice by a high fat/high cholesterol diet.3)(middle-dose) Xiao Zhi Tang had significantly therapeutic effects against hyperlipidemia, obesity.nonalcoholic fatty liver, insulin resistance, and could significantly increase the GLP-1level, slightly reduce leptin resistance, and preserve the beta-cell function.4) Further study could focus on the potential role of (middle-dose) Xiao Zhi Tangagainstosteoporosis besides its effect on weight control. |
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