An Integrated Research On FLD In TCM, Corresponding Prescription, Drug Use And Clinical Efficacy

Objective:FLD disease, which has become a global disease, is classified into two types as alcoholic fatty liver disease (AFLD) and non-alcoholic fatty liver disease (NAFLD). It has infected a considerable population in the world, demonstrating a global increasing trendency of incident rate. Among them, the NAFLD accounts for nearly 20% and in our country alcohol approximately takes the cause of liver cirrhosis's disease 5%~11%. Compared with the 80s, the disease incidence rate of alcoholic liver disease (ALD) approximately increased 30 times in the 90s. So far, there is still no explicit understanding to the cause of this disease, as well as its pathology developing process and the clinical prognosis. In addition, there has not been an effective medicine found to cure this disease. FLD, according to the clinical syndromes, pertains to the diseases of"Ji Zheng" (accumulation), "Xie Tong" (pains in flank), and the like in the scope of traditional Chinese medicine (TCM). Seeking the effective medicines from the traditional Chinese medicine is one of hot topic in clinical research.Following the medical principle of consistency in TCM, through the comprehensive study of modern literature concerning FLD in traditional Chinese medicine and the clinical practice, this study conducts an integrated research on FLD in TCM, its corresponding prescription, drug use and clinical cfficacy, discussing FLD's pathogenesis pathology, studying the medicine recipe of Compound Recipe Qi-Yin Granule (CRQG) and its integration mechanism. This study aims to supplement the data base of FLD in Chinese medicine and clinical research, to develope new ideas regarding prevention and treatment of FLD in Xinjiang and to lay the foundation for new drugs research.Methodology:This study is based on much literature review,summarizing the names of FLD in TCM, the clinical classification and the laws of drug use. Based on the survey of syndrome, this study sums up the specificities of FLD in traditional Chinese medicine.Through the clinical comparation study of phosphatidylcholine and the CRQGrespectively affecting FLD, observation of the before and after changes on the blood lipids, liver function indicators, waist circumference index, body mass index and changes in imaging, the clinical efficacy is discussed. What's more, through studying the effect when changing the doses of CRQG, plus or minus the amount of the Granule, the amount and the composition of the drug are to be determined. And the methods of studying related literature is to be employed to analyse the mechanism of the recipe. A pharmacodynamic study is conducted on the affection produced by CRQG to the Liver pathology and the biochemical parameters of the experimental rats with FLD, meanwhile to analyze the mechanism of CRQG.Results:The modern TCM literature review on FLD: The modern TCM literature review on FLD shows that the modern medicine universally holds the names for FLD as"Xie Tong"(pains in flank),"Ji Ju"(accumulation), the most commonly witnessed type are liver depression and Qi stagnation, liver depression and liver deficiency, phlegm stasis and meridian obstructing, Qi-stagnancy and blood stasis. According to TCM classification of pathological factors, phlegmatic hygrosis, liver depression, Qi stagnation, blood stasis, liver deficiency, humid heat are the most important factors. According to the organs'classification, the liver, spleen and kidney are most related. According to the classification of asthenia and sthenia, the most common actual situation is the mixture of asthenia and sthenia. The most commonly used drugs are as follows: Danshen, Alisma, Chaihu, Hawthorn, Shouwu, Capillaris, Radix, Atractylodes macrocephala, and Cassia. Study on characteristics of symptom classification of the patients with FLD inXinjiang: the syndrome characteristics of the disease in terms of frequency appears as follows: poor appetite and gastric cavity expansion, uncomfortable right flank, prick pain under the right flank, re-trapped body fat, sore waist and tinnitus, diarrhea and runny stool, stool soft, upset and dry mouth, dizziness, deficiency of limbs. The possible infectious organs are: spleen, liver and kidney. The factors contained in the pathological symptoms are as follows: spleen, liver depression, blood stasis, pathogenic damp. The order of the pattern of syndrome among the patients with FLD in Xinjiang goes as follows: liver depression and stagnation of phlegm - Type, stagnation of liver-QI with deficiency of the spleen - Type, and liver kidney-yin deficiency - Type. Further more, the TCM syndrome distribution is closely related to nationality, age and the amount of alcohol. Han patients mainly fall to stagnation of liver-QI with deficiency of the spleen - Type, while Uygur patients mainly fall to the liver depression and stagnation of phlegm - Type. The incidence rate of FLD is significantly high between 30 and 50 years old. In addition, the incidence of alcohol-type FLD is significantly high.Study on the recipe of CRQG: The results of the study on recipe shows that the high-dose group displays the best effect in the experiment on rats with high-fat diet-induced FLD, with regard to the effect on the blood-fat, the liver function and the liver histological changes, compared with the other different dose of the CRQG, namely, the moderate and the low dose groups. Detecting the effects when changing the amount of the Granule, for instance, substracting respectively the amount of different group of adjuvant bringing about different effectiveness, it is found that the integrated group serves best when compared with the other groups.Clinical research: Clinical research shows that the effects of the CRQG on AFLD (Liver depression and spleen deficiency type) indicates that it can effectively improve the clinical symptoms, significantly reduced ALT, ALP and triglyceride, cholesterol tests and other indicators, and in imaging there is a great improvelment. Comparing the various indicators before and after treatment, significant difference is observed (P<0.05). While compared with the various indicators produced by CRQG group, in polyene phosphatidylcholine group, no statistical significance is found (P>0.05). In the treatment of non-alcoholic FLD (Liver depression and spleen deficiency-Type), compared with the controlled group,in improving the efficacy of TCM syndrome, liver type-B ultrasonic, triglyceride (TG), body mass index, insulin resistance index, statistical significant differences are found (P<0.05). In reducing ALT, AST, and CHOL, compared with the control group, no significant differences are found (P>0.05).Mechanisim study on CRQG: Experimental study shows that the Compound Recipe Qi-Yin Granule can significantly lower the serum total cholesterol (CHOL), the low density lipoprotein (LDL-C), the liver weight, the liver index (P<0.05), triglyceride (TG), alanine aminotransferase (ALT), body weight and increased high-density lipoprotein (HDL-C) in the rats with high fat diet-induced non-alcoholic FLD. Besides, a marked improvement in the fat on the livers of rats is observed (P<0.01). Compound Recipe Qi-Yin Granules of the low, the moderate and the high dose group, to a various extent, can reduce the content of the NAFLD serum leptin and insulin, and improve the state of insulin resistance. Compared with the Polyene Phosphatidylcholine group, there is no significant difference detected. Conclusion:Synthesis of traditional Chinese medicine literature concering the FLD disease, the characteristics of the syndrome may be concluded as follows: This disease pertains to"Flankache" and "Accumulation"in traditional Chinese medicine , The focus of the disease lies in the liver, closely related to spleen, kidney, gall bladder and the other organs. The main pathological factors include the spleen deficiency, liver depression, Kidney and other organ dysfunction and phlegm, heat, blood stasis, etc. Its clinical syndrome demonstrates as a type of mixture of asthenia and sthenia. The clinically used drugs mainly serve for the spleen and kidney. In addition to the above, the Uygur patients in Xinjiang have their own characteristics of its geographical features, that is, liver depression and stagnation of phlegm, pertaining to sthenia syndrome. Liver and kidney-yin deficiency and endogenous dryness-evil dominate in Xinjiang.The different set of pharmacodynamic animal experiments with the CRQG indicate that the original integrated group makes the best effect with regard to improving the blood lipids and liver function in the experimental rats with FLD, when respectively adding or substracting the amount of different group of adjuvants, which bring about different effectiveness, according to the principle of"Jun Chen Zuo Shi"(the principal, adjuvant, auxiliary and conductant ingredirnts). The clinical observation suggests that the CRQG has an obvious effect on the patients in improving the liver function, blood lipids, serum insulin, body mass index, and the grade of type-B ultrasonic of FLD. And it also presents a significant effect in improving the clinical symptoms, better than the control drugs. The treatment to the high-fat diet-induced experimental non-alcoholic FLD in rats partially reveals the potential effective mechanism of the CRQG: regulation of lipid metabolism; removal of free radicals, stress on the antioxidant and lipid peroxidation; stability and restoration of normal structure of liver cells.