| Background: Fatty liver is a liver disease with excessive accumulation of lipid in liver cells due to various reasons.It is now the second largest liver disease after viral hepatitis.Clinically,the common causes of fatty liver are alcoholism,obesity(high fat diet),malnutrition,diabetes and so on.With the economic developing of our country,the living condition of the people has improved these years.The proportion of high-fat foods such as meat,meat products and deep-fried foods has continuously increased in their daily diets,leading to a significant increase in the incidence of obesity,fatty liver and hyperlipidemia,And the incidence of the growing trend of younger people,which seriously threaten people's health.The liver is an important organ of energy metabolism,which is the central organ of lipid synthesis and catabolism.Under normal circumstances,the fat in the gut is enzymaticlyhydrolized into free fatty acids and glycerol and then transferinto the blood stream.The liver can absorb blood free fatty acid in the synthesis of three acyl glycerin,and combined with apolipoprotein lipoprotein release to blood formation.Generally,fat is not stored in the liver,it is stored in adipose tissue which can be mobilized to the liver when human is hungry or sugar supply is insufficient.However,it can break the balance of liver lipid metabolismafter a long period of excessive intake of high fat food.This will lead tooveraccumulation of lipid in the liver and formation of fatty liver.For a long time,it can induce a series of inflammatory reactions in the liver and cause liver damage.Due to the complex pathogenesis of non-alcoholic fatty liver disease,the current treatment effect of western medicine is not good,and some drugs may have adverse reactions,which limit the application of western medicine.Compound Ganzao Ning Granule is a pure Chinese medicine preparation developed by Professor Ling Changquan of Shanghai Changhai Hospital.The prescription is composed of jujube,yam,hawthorn,bergamot,lotus leaf and corn stigma.It has the effect of soothing liver.Clinical application found that it has good curative effect on liver diseases such as fatty liver and cirrhosis.All the medicines in the prescription are homologous to medicine and food,and are suitable for long-term use.Objective:In the clinical study,the results of Ganzaoning granule in the treatment of patients with non-alcoholic fatty liver disease were observed,so as to understand the efficacy of this prescription and lay a foundation for later clinical studies.In the experimental study,the intervention effect of Ganzaoning granule on non-alcoholic fatty liver disease induced by high-fat diet in rats was observed,and the possible mechanism of Ganzaoning granule in the treatment of non-alcoholic fatty liver disease was explored,so as to provide basis for subsequent studies.Methods: In the clinical study,395 patients with non-alcoholic fatty liver disease were given Ganzaoning granules for 6 months,and the clinical efficacy of Ganzaoning granules in the treatment of non-alcoholic fatty liver disease was observed by comparing the changes of body mass index(BMI),abdominal circumference,TCM symptom evaluation,liver function,blood lipid and liver b-ultrasound before and after the treatment.Experimental research section,60 male SD rats were randomly divided into 6 groups.Except the 1 set as blank control group,the rest are to establish nonalcoholic fatty liver model of rats,divided into the experimental model group,atorvastatin group and Ganzaoning granule(low,middle and high dose)group.After taking different dosing method,observing the corresponding drugs on rat liver function,blood fat,liver index,hepatic pathological changes and the effect of the levels of TNF-?,IL-6,IL-1? in serum and the changes in m RNA and protein expression levels of SREBP-1c,LXR?,ACC1,FAS,PGC-1? in liver tissues of rats were detected before and after the intervention.We also observed the changes in protein expression levels of p-AMPK? and p-NF-?B.Results: The results of the clinical study showed that,there were no significant differences in body mass index(BMI)before and after treatment,while there was statistical significance in abdominal circumference.The main single symptoms of TCM were obviously improved,with an overall effective rate of 83.29%.The levels of TC,TG and LDL-C were all reduced after the treatment,while there was no significant change in the levels of HDL-C,when comparisons were made between pre-treatment and post-treatment.Before treatment,the patients were assessed as moderate NAFLD by ultrasonography,with a total of 252 cases,accounting for 63.80%.However,after treatment,there were mainly diagnosed as mild NAFLD,with a total of 311 cases,accounting for 78.73%.The results of the experimental research showed that,after feeding high fat diet for 6 weeks,the body weight,liver wet weight and liver index in the high fat diet model group were significantly higher than that in the blank group.The levels of TC,TG,AST and ALT in serum increased significantly,the level of HDL-C decreased significantly,and the level of TNF-?,IL-6 and IL-1?was significantly higher.After feeding high fat diet for 12 weeks,the body weight,liver wet weight and liver index in the high fat diet model group were significantly higher than that in the blank group.The levels of serum TC,TG,AST and ALT increased significantly,the level of HDL-C decreased significantly,and the level of TNF-?,IL-6 and IL-1?was significantly higher.The above data indicate that long term high fat diet had caused abnormal lipid metabolism in rats,and the fat was deposited in the liver and had a certain inflammatory response.At the same time,RT-PCR results showed that the relative expression level of SREBP-1c,LXR?,ACC1 and FAS m RNA which correlated with lipid accumulation were up-regulated,and the relative content of PGC-1? m RNA in the AMPK/PGC-1? and AMPK/NF-?B pathway decreased significantly.Western-blot results indicated that the relative levels of lipid accumulation related protein that SREBP-1c,LXR?,ACC1 and FAS increased significantly,and the relative content of p-AMPK?,PGC-1?,and p-NF-?B in the AMPK/PGC-1? and AMPK/NF-?B pathway decreased significantly.Compared with the model group,the levels of TG,TC,AST and ALT in serum were increased,the level of HDL-C was increased,and the levels of TNF-?,IL-6 and IL-1? were significantly decreased in the low,middle and high dose groups of Ganzaoning Granule.The results of microscopic examination showed that Ganzaoning Granule could significantly reduce the liver tissue fat and inflammation,and the liver lobule and central vein were basically restored to normal.RT-PCR results showed that different doses of Ganzaoning granules could decrease the relative levels of protein of SREBP-1c,LXR?,ACC1 and FAS m RNA.It also can increase the relative level of PGC-1-? m RNA in the AMPK/PGC-1? and AMPK/ NF-?B pathway.Western-blot results showed that different doses of Ganzaoning Granule can decrease the relative levels of protein of SREBP-1c,LXR?,ACC1 and FAS.It also can increase the relative level of p-AMPK?,PGC-1?,p-NF-?B protein in AMPK/PGC-1? and AMPK/NF-?B pathway.Conclusion: Ganzaoning Granule has a good effect in the treatment of non-alcoholic fatty liver disease.The mechanism of its action may be realized through the following ways: 1.To activate of AMPK/PGC-1? pathway,and decrease relative level of SREBP-1c,LXR?,ACC1 and FAS,reduce the TC and TG content in serum,the content of HDL-C increased,so as to improve the metabolism of lipids,reduce lipid deposition in the liver.2.To activate the AMPK/NF-?B pathway and reduce the levels of TNF-?,IL-6 and IL-1? in the serum,and alleviate the inflammatory reaction in the liver. |
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