实用医学杂志 ›› 2023, Vol. 39 ›› Issue (3): 285-297.doi: 10.3969/j.issn.1006⁃5725.2023.03.004

• 基础研究 • 上一篇    下一篇

自噬对激素性股骨头坏死大鼠的作用效果分析 

屈肖肖1 乔庆阳1 陈宁1 宋同阳1 李瑜2 刘树义1    

  1. 1 西安医学院临床医学院(西安 710021);2 西安医学院第二附属医院耳鼻咽喉科(西安 710038)

  • 出版日期:2023-02-10 发布日期:2023-02-10
  • 通讯作者: 刘树义 E⁃mail:doclsy@163.com
  • 基金资助:
    陕西省教育厅专项科学研究计划项目(编号:19JK0768);陕西省大学生创新创业训练计划项目(编号:S202111840038);
    西安医学院大学生创新创业训练计划项目(编号:121521038)

Effect of autophagy on steroid ⁃induced osteonecrosis of femoral head in rats

QU Xiaoxiao*,QIAO Qing⁃ yang,CHEN Ning,SONG Tongyang,LI Yu,LIU Shuyi.   

  1. Clinical Medicine of Xi′an Medical UniversityXi′an 710021China
  • Online:2023-02-10 Published:2023-02-10
  • Contact: LIU Shuyi E⁃mail:doclsy@163.com
  • Supported by:


摘要:

目的 探究自噬干预对激素性股骨头坏死大鼠股骨头坏死的治疗效应。方法 18 SPF SD 大鼠,随机分为模型组(M 组)、自噬阻断组(M⁃3⁃MA 组)及自噬激动组(M⁃Rap 组),分别给予甲泼尼 龙、甲泼尼龙+3⁃甲基腺嘌呤(3⁃MA)、甲泼尼龙+雷帕霉素(Rapamycin),8 周后经腹主动脉采血,测定血脂、 一氧化氮(NO)、内皮型一氧化氮合酶(endothelial nitric oxide synthase,eNOS)及内皮素 1(endothelin⁃1 ET⁃1)含量;股骨头取材后,Western blot 检测 LC3Ⅱ/Ⅰ p62 的表达。结果 M 组、M⁃3⁃MA 组及 M⁃Rap 股骨头坏死率分别为 66.67%、100%、33.33%,与 M 组比较,组间比较 M⁃3⁃MA 组平均股骨头坏死表面积更 大,而 M⁃Rap 组更小,差异有统计学意义(P < 0.05);与 M 组比较,M⁃3⁃MA 组大鼠股骨头内 LC3Ⅱ/Ⅰ蛋白 表达量降低、p62 蛋白表达量升高,血中甘油三酯(TG)、总胆固醇(TCH)、低密度脂蛋白(LDL)及 ET⁃1 量升高,高密度脂蛋白(HDL)、eNOS NO 含量降低,M⁃Rap 组大鼠股骨头内 LC3Ⅱ/Ⅰ蛋白表达量增加、 p62 蛋白表达量降低,血中 TG、TCH、LDL ET⁃1 含量降低,HDL、eNOS NO 含量升高,差异均有统计学意 义(P < 0.05)结论 自噬干预可通过调节脂质代谢和促进血管内皮损伤修复来改善 SANFH 的发生率, 局限坏死病灶范围,是SANFH 治疗的新方向。

关键词:

自噬, 激素性股骨头坏死, 血脂, 一氧化氮合酶, 内皮素

Abstract:

Objective The research aimed to investigate the effect of autophagy intervention on femoral head necrosis in rats with steroid⁃induced osteonecrosis of femoral head. Methods Eighteen SPF SD rats were randomly divided into three groups:model group(M),autophagic block group(M⁃3⁃MA)and autophagic activation group(M⁃Rap),and then they were treated with methylprednisolone,methylprednisolone + 3⁃methyladenine(3⁃ MA),methylprednisolone + rapamycin,respectively. After 8 weeks,blood samples were collected from abdominal aorta for determination of blood lipid and endothelial nitric oxide synthase(eNOS),nitric oxide(NO)and endo⁃ thelin⁃1(ET⁃1)content. After harvesting the rat femoral head,the expression of LC3Ⅱ/Ⅰ and p62 was detected by Western blot. Results The necrosis rate of femoral head in M,M ⁃3⁃MA and M ⁃Rap groups was 66. 67% 100% and 33.33%. Compared with group M,the mean necrotic surface area of femoral head was larger in group M⁃3⁃MA and smaller in group M⁃Rap. The difference was statistically significant(P < 0.05). Compared with group M,the LC3Ⅱ/Ⅰ expression in M⁃3⁃MA group was decreased and the expression of p62 was increased,the levels of TG,TCH,LDL and ET⁃1 in blood were all increased,but the contents of HDL,eNOS and NO were decreased in M⁃RAP group,the expression of LC3Ⅱ/Ⅰ protein was increased,the expression of p62 protein was decreased the levels of TG,TCH,LDL and ET⁃1 in blood were decreased,but the HDL,eNOS and NO increased. All the differences were statistically significant(P < 0.05). Conclusion Autophagy intervention can improve the inci⁃ dence of SANFH by regulating lipid metabolism and promoting the repair of vascular endothelial injury,and limit the scope of necrotic lesions,which is a new direction of SANFH treatment.

Key words:

autophagy, steroid ? induced necrosis of femoral head, blood lipid, nitric oxide syn? thase, endothelin