| With the morbidity of non-alcohol fatty liver disease increasing year by year, NASH is critical in the development of liver fibrosis and liver failure, which has became a new challenge in the field of liver diseases research. At present, there is still no specific medicine for NASH, but the Chinese traditional medicine has its advantage on NASH. With many years of clinic research and experience, a recipe of HTQF (hua tan qu shi huo xue fang) has been formulated by our tutor and that has a good effect. What's more, after years of clinical application, the effect is inspiring. To further clarify the clinical efficacy and therapeutic mechanism, this study is implemented.Objective:to implore the clinical efficacy and therapeutic mechanism of HTQF. to provide the theoretic evidence for the clinic application of HTQF.Methods:the study was divided into two parts.1. Clinical research:A multi-center randomized controlled clinical study was done on202NASH patients from four sub-centers which were divided into the treatment group and the control group. Base on the health education, diet and exercise, the treatment group was administrated HTQF one dose per day and the control group polyene phosphatidylcholine three times per day. The course of the study was three months and the follow-up was three months too. After that the ALT, AST, TC, FFA of the liver homogenate, the ratio of liver/spleen CT values, the signs and symptoms, Body Mass index were observed to evaluate the clinical efficacy of HTQF on NASH.2.experimental study:the ALT, AST, TG, TC, FFA of the liver homogenate, the liver histopathology, the liver cytochrome P4502E1, the PPARa-mRNA were detected as the observation targets according to the NASH pathogenesis.72male rats were divided into6groups randomly, the normal group, the model group, the polyene phosphatidylcholine group, the HTQF high, medium and low dose group. NASH rat model was duplicated with high fat diet and tetracycline intraperitoneal injection. The animals were sacrificed after7weeks. After the blood collected from the abdominal aorta, the liver wet weights were measured and the liver specimens kept. The liver index and the histopathological changes (light microscopy and electron microscopy) were observed. The ALT, AST, TC, FFA of the liver homogenate, the liver cytochrome P4502E1, the PPARa-mRNA and so on were investigated too. Result:the results of the clinical research and experimental study are displaced as follow.1. Clinical research①The levels of serum ALT and TG, in treatment and control group, declined significantly after therapy (P<0.05), which indicated that the two groups were all effective in protecting liver function, reducing enzymes and decreasing TG, while the former groups were superior to the latter group (P<0.05). The ratio of liver/spleen CT values, in treatment and control group, were reduced significantly after therapy (P<0.05) and the former groups were superior to the latter group too (P<0.05)②The BMI, in treatment and control group, declined significantly after therapy (P<0.05), but groups comparison showed no difference in statistics (P>0.05),which indicated that the two groups were all effective in decreasing BMI. Integration of signs and symptoms in treatment and control group declined significantly after therapy (P<0.05) and the former groups were more effective in ameliorating symptoms, such as heavy sensation in the limbs and body, hypochondriac distention and pain, abdominal fullness and distention, eating less, anorexia and loose stool (P<0.05)2. Experimental study①Treatment and model group comparison The content of liver index, serum ALT, AST, TC, TG and liver homogenate FFA, in treatment and control group, declined significantly at different level, after therapy (P<0.05), with the high-dose and medium-dose HTQF the most effective (P<0.01, P<0.05). The expression of CYP2E1-mRNA in hepatic tissue were all depressed in high-dose, medium-dose and low-dose HTQF and Polyene group (P<0.01), while the expression of PPARa-mRNA in hepatic tissue were elevated in high-dose and medium-dose HTQF group (P<0.01)②High-dose, medium-dose HTQF and Polyene group comparison When compared with Polyene group, several indexs changed significantly, which included ameliorated liver wet weight and histopathology, decreased level of serum ALT, AST, TC, TG and liver homogenate FFA, depressed CYP2E1-mRNA and elevated PPARa-mRNA(P<0.05), with no significantly different among the two groups of HTQF (P>0.05)③pathology The degree of steatosis, under light microscope, had significant difference between high-dose or medium-dose HTQF group and model group (P<0.01). There were significant differences when comparing either positive control (P<0.05), medium-dose HTQF group (P<0.05) or low-dose HTQF group (P<0.01) with high-dosed HTQSHXF group. There was significant difference between middle-dose and low-dose HTQF group too (P<0.05). Under electron microscope, there were significant difference of the elevated liver cells mitochondria bulk density (Vv), membrane density (δm) and rough endoplasmic reticulum membrane density (δm) when positive control group, high-dosed or middle-dosed HTQSHXF group compared with model group (P<0.05).There were significant difference of the decreased lipid drops bulk density (Vv) and mitochondrion specific surface (δ) too. While high-dose HTQF was superior to the medium-dose HTQF group and Polyene control group (P<0.01) with no significant difference between the latter two groups.Conclusion:As regarding to reducing the ALT, TG of the serum, raising the ratio of liver/spleen CT values, improving the clinical symptoms, the HTQF group was superior to the polyene group on NASH of phlegm and stasis. HTQF and polyene both can relieve the BMI. By far there are no side effect of HTQF on NASH of phlegm and stasis and HTQF is a safe and effective recipe. Using high fat diet and tetracycline intraperitoneal injection to duplicate NASH rat model is an ideal method, which is time saving and has high success rate. By reducing the wet liver weight, decreasing the index of liver, lowering the ALT, AST, TC, TG of serum and the FFA of liver homogenate, and improving the liver histopathology, HTQF has the good effect of anti-fatty liver. HTQF can induce the expression of PPARa-mRNA and correct the lipid metabolism disorders. At the same time HTQF can suppress the expression of CYP2E2-mRNA to prevent the lipid peroxidation. By protecting liver damage through preventing lipid peroxidation, HTQF can lower blood lipids, protect liver function and reduce the lever of liver transminases, so as to resist the formation of fatty liver, which may be one of its mechanism on NASH. HTQF can reduce the liver fat deposition. By increasing the mitochondria cristae and its number, improving the degranulation of rough endoplasmic reticulum, protecting the mitochondria and endoplasmic reticulum, restoring its morphology and function, enhancing the energy metabolism of the liver cells, HTQF owns the curative effect on NASH. |
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