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靶向特异基因小干扰RNA预防乙醇性股骨头坏死的研究 被引量:15

Prevention of alcohol-induced osteonecrosis of femoral head in rabbits by small interfering RNA targeting specific gene by gavage
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摘要 目的观察靶向PPARγ基因小干扰RNA(siRNA)预防灌胃法家兔乙醇性股骨头坏死的效果。方法将96只家兔随机分为4组,每组24只。N组:灌胃法给予生理盐水10ml/(kg·d)。M组:灌胃法给予烈性酒(含乙醇度46%,V/V)10ml/(kg·d);S组:实验1、3、5个月第1天,随机选择侧别手术,穿刺注入股骨头内25p,1siRNA重组腺病毒,同M组灌酒;c0组:同s组手术,同M组灌酒,不注入siRNA重组腺病毒。于2、4、6个月末分批处死家兔,观察血清学和股骨头组织病理学变化。结果实验6个月时,N、M、CO、S组血清甘油三酯含量分别为(1.21±0.12)、(4.59±1.58)、(4.63±1.17)、(4.32±1.20)mmol/L;总胆固醇含量分别为(2.35±0.33)、(19.59±1.58)、(20.13±1.17)、(18.32±1.20)mmol/L;脂肪细胞平均直径分别为(40.89±2.41)、(48.65±2.93)、(49.45±2.63)、(42.52±2.57)μm;骨小梁面积分数分别为(41.80±2.47)%、(30.70±2.86)%、(29.80±2.69)%、(41.60±2.87)%;空骨陷窝计数分别为(12.30±1.73)%、(22.40±1.52)%、(23.10±1.62)%、(11.70±1.46)%;PPARγ表达量分别为(0.29±0.05)、(0.66±0.12)、(0.61±0.15)、(0.33±0.05);骨钙素mRNA表达量分别为(0.92±0.07)、(0.19±0.11)、(0.23±0.08)、(0.88±0.11);PPAR~蛋白表达量分别为(0.75±0.08)、(1.60±0.11)、(1.55±0.12)、(0.65±0.05)。M、CO组病理变化明显,髓内造血组织减少,脂肪细胞增殖肥大,骨小梁变细、稀疏、部分断裂;S组股骨头内最大脂肪细胞平均直径、空骨陷窝计数、骨坏死发生率、PPARγ基因与蛋白表达量均明显低于M、CO组(P〈0.01,P〈0.05),S组与N组差异无统计学意义(P〉0.05)。结论靶向PPARγ基� Objective To observe the effect of small interfering RNA (siRNA) adenovirus vectors targeting PPARγ to prevent the alcohol-induced osteonecrosis of the femoral head (ONFH) in rabbits. Methods Ninety-six rabbits were randomly divided into four groups. In group N, normal saline (10 ml/kg every day) was poured into stomach. In group M, the strong wine (the volume fraction was 46% alcohol, 10 ml/kg every day) was poured into stomach. In group S, under the randomly selected side and anesthe- sia, the animals were injected with 25 μl siRNA adenovirus drip into the femoral head and then the punc- ture hole was closed on the 1st day at the 1st, 3rd and 5th month of the experiment, and at the same time the strong wine (the volume fraction was 46% alcohol, 10 ml/kg every day) was poured into stomach. In group CO, animals were treated with the same method as the group S, but not injected with siRNA adenovi- ms drip. The animals were sacrificed in batches at 2nd, 4th and 6th month after the experiment. The serol- ogy and pathological changes of the femoral head were studied. Results At the 6th month, the triglyceride (TG, mmol/L) contents in groups N, M, CO and S were (1.21 ±0.12), (4.59 ±1.58), (4.63± 1.17) and (4. 32 ± 1.20), the cholesterol levels ( CHO, mmol/L) were (2. 35 ± 0. 33 ), ( 19. 59 ± 1.58), (20. 13 ± 1. 17) and (18.32 ± 1.20), the average diameter of the max adipoeyte (ixm) was (40. 89 ±2. 41), (48.65 ±2.93), (49.45 ±2. 63) and (42. 52 ±2. 57), the trabeculace area fraction was (41.80 ±2. 47)%, (30. 70 ±2. 86)%, (29. 80 ±2. 69)% and (41.60 ±2. 87)%, the percentage of empty osteocyte lacunae was (12.30 ± 1.73)%, (22.40 ± 1.52)%, (23.10 ± 1.62)% and (11.70 ± 1.46)%, the expression levels of PPARγ mRNA were (0. 29 ±0. 05), (0. 66 ±0. 12), (0. 61 ±0. 15) and (0. 33 ±0. 05), the expression levels of osteocalcin mRNA were (0. 92 ±0. 07), (0. 19 ±0. 11 ),
出处 《中华实验外科杂志》 CAS CSCD 北大核心 2011年第4期611-614,共4页 Chinese Journal of Experimental Surgery
基金 基金项目:国家自然科学基金资助项目(30672128)
关键词 SIRNA PPARΓ 乙醇 股骨头坏死 家兔 预防 siRNA PPARγ Alcohol Osteonecrosis of femoral head Rabbit Prevent
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