1114 Chinese Journal of Pathophysiology 2013 29 6 1114-1118 1000-4718 2013 06-1114-05 * 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 1 130032 2 510602 3 511356 4 510663 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 < 0. 05 P < 0. 01 db /db db /db R363 A doi 10. 3969 /j. issn. 1000-4718. 2013. 06. 026 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 130032China 2 Center of Hepatopathy458th Hospital of PLAGuangzhou 510602China 3 Guangzhou Knockim Pharmacy Co. Ltd. Guangzhou 511356China 4 Guangzhou Cell-Gene Biotech Co. Ltd. Guangzhou 510663China. E-mail 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 < 0. 05 or P < 0. 01. 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 2013-01-03 2013-04-10 * No. 2011ZX09401-307 No. 2011Q - P033 Tel 020-87796965 E-mail zqy966@ 126. com
1115 S- NAFL 5-9 NAFLD 400 mg / kg 10 6 2. 2 检测指标 db /db 2. 2. 1 体重和肝脏指数 6 12 h % = / 100% 2. 2. 2 7 ALT TC triglyceride TG db /db low-density lipoprotein LDL 2. 2. 3 葡萄糖水平和静脉葡萄糖耐量试验 ( intravenous glucose tolerance test,igtt) 2 1 NAFLD IGTT 1 2. 2. 4 组织形态学检测 1. 1 动物 db /db db /m O HE 1. 2 材料 3 SPSS 13. 0 LY005 MT-Cel-Lytics ± mean ± SD BCA-100 P < 0. 05 D12331Research diets 1 db /db 2 2. 1 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 6 1 200 mg /kg P > 0. 05 1 400 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 63. 27 ± 5. 28 62. 32 ± 5. 70 61. 84 ± 5. 53 61. 30 ± 5. 70 61. 21 ± 5. 32 60. 31 ± 4. 33 59. 71 ± 4. 01 Medium dose 63. 18 ± 8. 94 62. 38 ± 8. 76 63. 14 ± 8. 07 62. 26 ± 7. 85 61. 96 ± 7. 99 61. 67 ± 7. 95 60. 85 ± 7. 72 High dose 62. 43 ± 6. 02 61. 85 ± 6. 18 61. 31 ± 6. 56 60. 38 ± 6. 47 59. 95 ± 6. 54 59. 28 ± 6. 49 58. 89 ± 6. 59 Saline control 62. 81 ± 6. 28 62. 87 ± 6. 54 63. 02 ± 6. 61 62. 68 ± 6. 63 62. 06 ± 6. 60 61. 96 ± 6. 92 61. 84 ± 7. 19 Positive drug 63. 10 ± 5. 45 62. 71 ± 6. 21 62. 15 ± 6. 38 61. 17 ± 6. 33 60. 39 ± 6. 19 60. 27 ± 5. 94 59. 66 ± 5. 88 The weight of normal db /m mice was 21. 80 ± 1. 19 g. 6 P < 0. 01 P > 0. 05 2 35. 41% 2 db /db 3 2. 1 TC TC 3 TC
1116 2 P < 0. 01 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 4. 50 ± 1. 08 Mean ± SD. n = 10 Medium dose 3. 88 ± 0. 84 High dose 3. 96 ± 0. 66 Saline control 3. 78 ± 0. 67 Low dose 1. 64 ± 0. 15 1. 74 ± 0. 20 1. 55 ± 0. 19 ** Positive drug 3. 69 ± 1. 22 Medium dose 1. 68 ± 0. 20 1. 69 ± 0. 24 1. 44 ± 0. 12 ** High dose 1. 75 ± 0. 15 1. 62 ± 0. 21 1. 36 ± 0. 18 ** 3 db /db TC Saline control 1. 68 ± 0. 14 1. 84 ± 0. 16 1. 80 ± 0. 11 Table 3. The effect of betaine on serum TC level in db /db mice Positive drug 1. 68 ± 0. 14 1. 48 ± 0. 16 1. 34 ± 0. 11 ** Mean ± SD. n = 10 Serum LDL level in normal db /m mice was 0. 46 ± 0. 15 Low dose 5. 05 ± 1. 46 4. 50 ± 0. 92 4. 07 ± 0. 49 Medium dose 5. 16 ± 1. 39 4. 61 ± 1. 61 3. 67 ± 0. 58 ** High dose 5. 14 ± 1. 17 4. 46 ± 1. 64 3. 32 ± 0. 72 ** Saline control 5. 06 ± 1. 55 4. 90 ± 1. 64 4. 51 ± 1. 17 Positive drug 5. 00 ± 1. 27 3. 32 ± 0. 43 * 3. 04 ± 0. 41 ** Serum TC level in normal db /m mice was 2. 14 ± 0. 22 * P < 0. 05 ** P < 0. 01 vs saline control. ** P < 0. 01 vs saline control. 2. 4 ALT ALT 6 ALT P < 0. 05 6 2. 2 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 233. 78 ± 98. 88 224. 89 ± 60. 71 125. 44 ± 22. 57 * Mean ± SD. n = 10 Medium dose 224. 17 ± 93. 28 212. 60 ± 103. 33 106. 88 ± 19. 22 * High dose 213. 75 ± 48. 95 158. 50 ± 28. 24 103. 25 ± 25. 55 * Low dose 1. 49 ± 0. 42 1. 75 ± 0. 59 1. 74 ± 0. 42 Saline control 190. 44 ± 87. 82 176. 63 ± 59. 32 131. 00 ± 36. 46 Medium dose 1. 41 ± 0. 22 1. 69 ± 0. 59 1. 59 ± 0. 24 Positive drug 185. 50 ± 53. 85 136. 75 ± 51. 35 89. 00 ± 26. 05 * High dose 1. 35 ± 0. 36 1. 56 ± 0. 49 1. 68 ± 0. 43 Serum ALT level in normal db /m mice was 34. 17 ± 4. 26 Saline control 1. 41 ± 0. 46 1. 75 ± 0. 50 1. 70 ± 0. 54 U /L. P < 0. 05 vs saline control. Positive drug 1. 50 ± 0. 43 1. 76 ± 0. 60 1. 55 ± 0. 52 Serum TG level in normal db /m mice was 1. 75 ± 0. 18 3 db /db 6 IGTT 30 min 2. 3 LDL db /m db /db LDL 6 7 LDL Table 7. 7 6 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 8 8. 18 ± 1. 86 16. 21 ± 3. 38 17. 76 ± 5. 47 12. 55 ± 5. 45 10. 28 ± 2. 88 Medium dose 9 7. 52 ± 1. 17 15. 43 ± 3. 16 16. 88 ± 6. 95 12. 49 ± 6. 95 9. 16 ± 3. 14 High dose 8 7. 88 ± 1. 94 16. 00 ± 1. 82 20. 78 ± 1. 95 15. 98 ± 1. 47 7. 66 ± 1. 47 Saline control 7 7. 71 ± 1. 56 17. 90 ± 1. 33 23. 71 ± 3. 99 15. 06 ± 6. 53 10. 37 ± 3. 62 Positive drug 6 8. 48 ± 1. 97 15. 05 ± 3. 56 19. 25 ± 3. 27 12. 55 ± 3. 92 8. 80 ± 2. 97 4 6 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. The histological observation and lipid accumulation of the liver tissues in the mice 400. 1 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
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