| Purpose:According to Professor Lu Bingjiu’s clinical experiences of non-alcoholic steatohepatitis(NASH),the mind of promoting blood circulation and removing dampness was established.The clinical study aimed to evaluate the clinical efficacy and safety of the decoction of Huo xue qu shi.The experiment aimed to investigate the efficacy and mechanism of the decoction on rat model of NASH.Material and method:In the clinical study,the NAFLD patients were randomly divided into the experimental group and the control group.Besides of the basic treatment,the control group received silybinin, the experimental group received silybinin and the decoction.The before and after results of indexes including the TCM symptom integral meter, BMI,transaminase,serum lipid level,serum SOD,MDA,TNF-ɑ level and liver B-ultrasonic examination of the patients were compared to evaluate the clinical efficacy and safety of the decoction.In the experimental study,the rats which were fed with the purified high-fat diet to establish NASH model were randomly divided into 6 groups which were the control group,the model group,the high,medium and low dose group and the silybinin group.All the groups were intervened with the corresponding drug.The hepatic protection effect,serum lipid level regulation, anti-oxidation and the role of NF-κB signaling pathway were observed and the possible mechanism was discussed.Results:Experiment No.1 The clinical experiment of the decoction of Huo xue qu shi on NASH patients.1.the TCM symptom integral meterThe total effective rate of the experimental group was 86.67% whereas the control group was 70.00%, the difference was compared significant difference(p<0.05).2. The BMI,transaminase,serum lipid levelThe BMI,transaminase,serum lipid level(TG,TC)decreased significantly(p<0.05).The result of the experimental group was better than that of the control group(p<0.05).The VLDL level of the experimental group decreased significantly(p<0.05),whereas there was no significant difference in the control group(p> 0.05).3. Serum SOD, MDA, TNF-ɑThe serum TNF-ɑ, MDA of the both two groups decreased significantly after treatment(p<0.05), the result of the experimental group was better than that of the control group(p<0.05). The serum SOD of the both two groups increased significantly after treatment(p<0.05), the result of the experimental group was better than that of the control group(p<0.05).4.liver B-ultrasonic examinationThe effective rate of the control group was 46.67%,whereas the experimental group was70.00%.There was no statistic different between the two groups(p> 0.05).It meant that the experimental group was not better than the control group in the improvment of liver morphology.5. Comprehensive efficacy evaluationThe total effective rate of the control group was 46.67% whereas that of the experimental group was 73.33%.The difference was statistically significant(p<0.05). The result of the experimental group was better than that of the control group(p<0.05)6. Safety AnalysisThere were no side effects and adverse events occurring during the process.Experiment No.2 The experimental study of the hepatic protection and the regulation of the blood lipids of the decoction of Huo xue qu shi on NASH model.1. The general conditions and pathological morphologyThe body weight and liver wet weight of the rats in the model group increased significantly compared with the control group.The color of the liver was yellow and the volume increased. There was visible fat vacuoles and inflammatory cell infiltration in the cytoplasm according to light microscopy of liver tissue.NAS histopathologic score was more than 5 points which meant the successful modeling.The body weight and liver wet weight of the rats in all the intervention groups decreased after the treatment.The difference was statistically significant(p<0.05). The high dose group and the silibinin group decreased more significantly(p<0.05 or p<0.01) in steatosis, inflammation, and ballooning degeneration scores than those of other groups.2. liver function and serum lipid levelThe serum ALT, AST, TG, VLDL of the model group significantly increased compared with the control group whereas the indexes decreased significantly in all the intervention groups(p<0.05 or p<0.01), in which the high dose group decreased more significantly(p<0.05 or p<0.01).All the intervention groups had the trend to decreas the serum TC in rats, but not statistically significant.Experiment No.3 The experimental study of the anti-oxidation effect of the decoction of Huo xue qu shi on NASH model.1. SOD,MDA level in the liver tissueThe SOD activity in the liver of the model group decreased significantly(p<0.01)whereas all the intervention groups increased significantly(p<0.01).The MDA content in the liver of the model group increased significantly(p<0.01) whereas all the intervention groups decreased significantly(p<0.01).The result of the high dose group was better than that of the other groups(p<0.01 or p<0.01).2. The CYP2E1 m RNA and protein expression and distribution in the liver tissueThe CYP2E1 m RNA and protein expression of the rats in the model group increased significantly compared with the control group(p<0.01 or p<0.05). The indexes of the high,middle dose group and the silibinin group significantly decreased(p <0.01 or p <0.05).The results of the high dose group and the silibinin group were better than the other groups(p<0.01 or p <0.05).Experiment No.4 The experimental study of the regulation effect of NF-κB signaling pathway of the decoction of Huo xue qu shi on NASH model.The expression of NF-κB p65, TNFR1, TNF-ɑ m RNA and protein of the rats in the model group increased significantly compared with the control group(p<0.01 or p<0.05).The indexes of all the intervention groups decreased significantly(p<0.01 or p<0.05). The results of the high dose group and the silibinin group were better than the other groups(p <0.01 or p<0.05).Conclusion:1 The group of decoction of Huo xue qu shi plus silibinin can improve BMI, liver function,serum lipid levels, hepatic morphology and the clinical symptoms in the treatment of NASH.There were no side effects and adverse events occurring during the process.Reduction of the visceral fat accumulation.the eradication of free radical,the improvement of antioxidant ability and inhibition of inflammatory factors may be the mechanism.2 The decoction of Huo xue qu shi could treat NASH rats model according to reducing the weight of rats and liver wet weight, protecting hepatic function, regulating blood lipid,improving the pathological.3 The decoction of Huo xue qu shi can improve antioxidant ability of the liver tissue,embodied in improving the activity of SOD enzyme in the body and liver,the eradication of MDA in the body and liver, inhibiting the expression of CYP2E1 gene and protein in the liver,reducing the distribution of CYP2E1 protein.4 The decoction of Huo xue qu shi can improve anti-inflammatory ability of the liver tissue and inhibit the inflammation.There may be two mechanisms :(1) the reduction of the inflammatory factors including TNF-ɑ and NF-κBp65expression;(2)the regulayion of NF-κB signaling pathway.5 According to the comparison of the results,the effect of the high dose of the decoction of Huo xue qu shi was better than the medium and low dose. |
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