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只SPF级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和p62的表达。结果 M组、M-3-MA组及M-Rap组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含量升高,高密度脂蛋白(HDL)、e NOS及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及ET-1含量降低,HDL、e NOS及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。
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 endothelin-1(ET-1)content.After harvesting the rat femoral head,the expression of LC3Ⅱ/Ⅰand 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/Ⅰexpression 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/Ⅰprotein 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 incidence 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.
作者
屈肖肖
乔庆阳
陈宁
宋同阳
李瑜
刘树义
QU Xiaoxiao;QIAO Qingyang;CHEN Ning;SONG Tongyang;LI Yu;LIU Shuyi(Clinical Medicine of Xi′an Medical University,Xi′an 710021,China;不详)
出处
《实用医学杂志》
CAS
北大核心
2023年第3期285-288,297,共5页
The Journal of Practical Medicine
基金
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)。
关键词
自噬
激素性股骨头坏死
血脂
一氧化氮合酶
内皮素
autophagy
steroid⁃induced necrosis of femoral head
blood lipid
nitric oxide syn⁃thase
endothelin
作者简介
通信作者:刘树义,E-mail:doclsy@163.com。
