1115 S- NAFL 5-9 NAFLD 400 mg / kg 检测指标 db /db 体重和肝脏指数 6 12 h % = / 100% ALT TC triglyceride TG db /db low-density lipopro

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1 1114 Chinese Journal of Pathophysiology * db /db 刘光洁 1, 刘光泽 2, 兰丹 4, 陈媚娟 2, 廖汉雄 3, 刘海霞 4 4, 邹清雁 db /db NAFLD 50 7 db /db NAFLD 200 mg /kg 400 mg /kg 800 mg /kg 6 ALT TG TC LDL ALT TC LDL P < P < db /db db /db R363 A doi /j. issn Effect of betaine on liver injuries in aging db /db mice induced by lipids LIU Guang-jie 1 LIU Guang-ze 2 LAN Dan 4 CHEN Mei-juan 2 LIAO Han-xiong 3 LIU Hai-xia 4 ZOU Qing-yan 4 1 College of Computer Science and TechnologyChangchun Normal UniversityChangchun China 2 Center of Hepatopathy458th Hospital of PLAGuangzhou China 3 Guangzhou Knockim Pharmacy Co. Ltd. Guangzhou China 4 Guangzhou Cell-Gene Biotech Co. Ltd. Guangzhou China. zqy966@ 126. com ABSTRACTAIM To evaluate the effect of betaine on lipid metabolism disorder in inherited db /db mice with long-term nonalcoholic fatty liver disease NAFLD. METHODS Experimental NAFLD models were established by feeding the db /db mice with high-fat diet. Fifty 7-month-old db /db mice were randomly divided into 5 groups the mice in low medium and high dose groups were given betaine by intragastric administration at doses of 200 mg /kg400 mg /kg and 800 mg /kg for 6 weeksrespectively while the mice in saline control group and positive drug group were given normal saline and positive control drug respctively. All the animals were killedand serum alanine aminotransferase ALT triglyceride TG total cholesterol TC low-density lipoprotein LDL and glucose tolerance were detected. The pathological changes of the liver tissues were also observed. RESULTS Betaine significantly decreased the levels of ALTTC and LDL P < or P < The pathological changes of the liver tissues indicated that the content of lipid in the hepatocytes of betaine treatment groups was less than that in saline control group. CONCLUSION Betaine significantly improves the lipid metabolism and the liver function in the aging db /db miceand reduces the accumulation of lipid in the hepatocytes. KEY WORDSBetaine Nonalcoholic fatty liver disease db /db mice nonalcoholic fatty liver NAFL nonalcoholic fatty liver disease NAFLD NAFLD 1-4 betaine NAFLD * No. 2011ZX No. 2011Q - P033 Tel zqy966@ 126. com

2 1115 S- NAFL 5-9 NAFLD 400 mg / kg 检测指标 db /db 体重和肝脏指数 6 12 h % = / 100% ALT TC triglyceride TG db /db low-density lipoprotein LDL 葡萄糖水平和静脉葡萄糖耐量试验 ( intravenous glucose tolerance test,igtt) 2 1 NAFLD IGTT 组织形态学检测 1. 1 动物 db /db db /m O HE 1. 2 材料 3 SPSS LY005 MT-Cel-Lytics ± mean ± SD BCA-100 P < D12331Research diets 1 db /db 动物模型及分组 50 db /db 1 total cholesterol TC 3. 0 mmol /L alanine aminotransferase ALT 120 U /L db /db 800 mg /kg db /db mg /kg P > mg /kg Table 1. 1 Changes of weight among groups g. Mean ± SD. n = 10 Group 0 weeks 1 weeks 2 weeks 3 weeks 4 weeks 5 weeks 6 weeks Low dose ± ± ± ± ± ± ± Medium dose ± ± ± ± ± ± ± High dose ± ± ± ± ± ± ± Saline control ± ± ± ± ± ± ± Positive drug ± ± ± ± ± ± ± The weight of normal db /m mice was ± g. 6 P < P > % 2 db /db TC TC 3 TC

3 P < Table 2. The effect of betaine on liver index %. Mean ± SD. n = 10 LDL 5 5 db /db LDL Group Liver index Table 5. The effect of betaine on serum LDL level in db /db mice Low dose ± Mean ± SD. n = 10 Medium dose ± High dose ± Saline control ± Low dose ± ± ± ** Positive drug ± Medium dose ± ± ± ** High dose ± ± ± ** 3 db /db TC Saline control ± ± ± Table 3. The effect of betaine on serum TC level in db /db mice Positive drug ± ± ± ** Mean ± SD. n = 10 Serum LDL level in normal db /m mice was ± Low dose ± ± ± Medium dose ± ± ± ** High dose ± ± ± ** Saline control ± ± ± Positive drug ± ± * ± ** Serum TC level in normal db /m mice was ± * P < ** P < vs saline control. ** P < vs saline control ALT ALT 6 ALT P < TG 6 db /db ALT Table 6. The effect of betaine on serum ALT level in db /db mice TG 4 U /L. Mean ± SD. n = 10 4 db /db TG Table 4. The effect of betaine on serum TG level in db /db mice Low dose ± ± ± * Mean ± SD. n = 10 Medium dose ± ± ± * High dose ± ± ± * Low dose ± ± ± Saline control ± ± ± Medium dose ± ± ± Positive drug ± ± ± * High dose ± ± ± Serum ALT level in normal db /m mice was ± Saline control ± ± ± U /L. P < vs saline control. Positive drug ± ± ± Serum TG level in normal db /m mice was ± db /db 6 IGTT 30 min 2. 3 LDL db /m db /db LDL 6 7 LDL Table IGTT The results of IGTT of the mice at 6 weeks Mean ± SD Group n 0 min 15 min 30 min 60 min 120 min Low dose ± ± ± ± ± Medium dose ± ± ± ± ± High dose ± ± ± ± ± Saline control ± ± ± ± ± Positive drug ± ± ± ± ± HE

1117 50% 6 O 1 1 8 Low dose 10 5 5 5 Medium dose 8 6 3 4 High dose 8 7 0 3 Saline control 10 3 7 5 Positive drug 9 7 2 3 NAFL 6 NAFL 10 NAFL db /db db /db 10 d 4 6 1 3 db /db NAFLD Figure 1.

4 % 6 O Low dose Medium dose High dose Saline control Positive drug NAFL 6 NAFL 10 NAFL db /db db /db 10 d db /db NAFLD Figure 1. The histological observation and lipid accumulation of the liver tissues in the mice HE O TC TG 8 Table 8. The morphological changes of the hepatic tissues of the mice n = 10 Group Slight fatty Severe fatty Hydropic degeneration Focal necrosis degeneration degeneration S- S- S- TG

5 1118 S- 6 db / J. db TC LDL TG VLDL LDL VLDL LDL Ratziu VBellentani SCortez-Pinto Het al. A position statement on NAFLD /NASH based on the EASL 2009 special conference J. J Hepatol J A β- 4O Shea RSDasarathy SMcCullough AJ. Alcoholic liver disease J. Hepatology Comar KM Sterling RK. Drug therapy for non-alcoholic fatty liver diseasej. Aliment Pharmacal Ther ALT Kathirvel EMorgan KNandgiri G et al. Betaine improves nonalcoholic fatty liver and associated hepatic insu- ALT lin resistance a potential mechanism for hepatoprotection by betaine J. Am J Physiol Gastrointest Liver Physiol G1068-G Patrick L. Nonalcoholic fatty liver disease relationship to HE insulin sensitivity and oxidative stress. Treatment approaches using vitamin Emagnesiumand betainej. Al- 50% tern Med Rev J. O % O 9Duvnjak MTomasic VGomercic Met al. Therapy of nonalcoholic fatty liver disease current status J. J Physiol Pharmacol Suppl NAFLD 10Mukherjee S. Betaine and nonalcoholic steatohepatitis back to the future J. World J Gastroenterol Larter CZYeh MM. Animal models of NASH getting both pathology and metabolic context rightj. J Gastroenterol Hepatol Shen LFan JGShao Yet al. Prevalence of nonalcoholic fatty liver among administrative officers in Shanghai an IGTT epidemiological survey J. World J Gastroenterol Peluso GBarbarisi ASavica V et al. Carnitine an osmolyte that plays a metabolic rolej. J Cell Biochem db /db 14Shin OHMar MHAlbright CDet al. Methyl-group donors cannot prevent apoptotic death of rat hepatocytes induced by choline-deficiency J. J Cell Biochem

中草药 Chinese Traditional and Herbal Drugs 第 46 卷第 9 期 2015 年 5 月 1339 非酒精性脂肪性肝病 (nonalcoholic fatty liver disease,nafld) 是一种与胰岛素抵抗遗

中草药 Chinese Traditional and Herbal Drugs 第 46 卷第 9 期 2015 年 5 月 1339 非酒精性脂肪性肝病 (nonalcoholic fatty liver disease,nafld) 是一种与胰岛素抵抗遗 1338 中草药 Chinese Traditional and Herbal Drugs 第 46 卷第 9 期 2015 年 5 月九味肝泰胶囊对高脂饮食诱导大鼠非酒精性脂肪肝的治疗作用陈菲 1 2,, 艾国 3, 盛柳青 1, 麻佳蕾 1, 黄正明 1. 金华职业技术学院医学院, 浙江金华