南方医科大学学报

南方医科大学学报 ›› 2020, Vol. 40 ›› Issue (01): 104-109.doi: 10.12122/j.issn.1673-4254.2020.01.14

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基质金属蛋白酶-1、金属蛋白酶组织抑制因子-1在老年肌少症大 鼠中的表达及意义

朱师宇，吕安康，赵宇星，蒲 蝶，廖芷吟，孙 悦，陈金梁，肖 谦   

  • 出版日期:2020-02-19 发布日期:2020-01-20
  • 基金资助:

Expressions of matrix metalloproteinase-1 and tissue inhibitor of metalloproteinases 1 in skeletal muscles of aged rats with sarcopenia

  

  • Online:2020-02-19 Published:2020-01-20

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摘要： 目的 观察肌少症大鼠骨骼肌质量、力量的变化以及基质金属蛋白酶（MMP-1）、金属蛋白酶组织抑制因子（TIMP-1）及Ⅰ型胶原的表达。方法 11 只5 月龄SD大鼠作为成年对照组(YC组）；18只24月龄SD大鼠根据双能X线吸光测定得到的相对瘦质量（瘦质量%）分为两组，其中9只大鼠为老年对照组（OC组），9只大鼠为老年肌少症组（OS组），分组标准为YC组相对瘦质量较OS组高2SD；大鼠喂养4周后处死；电子抓力仪测量大鼠前肢抓力；HE染色和天狼星红染色观察大鼠腓肠肌细胞外基质变化；Western blot检测MMP-1、TIMP-1及Ⅰ型胶原的蛋白表达量。结果 老年对照组相对抓力低于成年对照组（P<0.01），瘦质量%与成年对照组无统计学差异（P>0.05），HE染色和天狼星红染色示细胞外基质较成年对照组增多，Ⅰ型胶原、TIMP-1的表达高于成年对照组（P<0.05），MMP-1的表达与成年对照组无统计学差异（P>0.05）；与老年对照组相比，老年肌少症组相对抓 力未见显著性差异（P>0.05），瘦质量%显著下降（P<0.01），HE染色及天狼星红染色示细胞外基质增多，Ⅰ型胶原、TIMP-1的表达增多（P<0.05），MMP-1的表达降低（P<0.05）。结论 增龄过程中骨骼肌MMP-1/TIMP-1失衡，影响细胞外基质代谢，导致细胞外胶原纤维增多，进而影响骨骼肌质量和功能，可能是肌少症发病的重要原因之一。

Abstract: Objective To investigate the changes of skeletal muscle mass and strength and the expressions of matrix metalloproteinase-1 (MMP-1), tissue inhibitor of metalloproteinases-1 (TIMP-1) and collagen-1 in the skeletal muscle of aged rats with sarcopenia. Methods With 11 young (6-month-old) SD rats as control group, 18 aged (25-month-old) SD rats were divided into two groups (n=9) according to the relative lean mass determined dual X-ray absorptiometry (DXA), namely aged control group and aged sarcopenia group (the relative lean mass was 2SD higher in aged control than in aged sarcopenia group. The forelimb grip strength of the rats was measured using an electronic grip strength meter. The extracellular matrix (ECM) of the rat’s gastrocnemius was observed with HE staining and sirius Red staining, and the protein expressions of collagen-1, MMP-1, and TIMP-1 in the muscular tissues were detected with Western blotting. Results Compared with the young rats, the aged control rats had significantly lower relative grip strength (P<0.01) and increased expressions of collagen-1 and TIMP-1 (P<0.05) and ECM content in the skeletal muscles, but the relative lean mass and MMP-1 protein expression were comparable between the two groups (P>0.05). Compared with the aged control rats, the aged sarcopenic rats had significantly lowered relative lean mass (P<0.01) and MMP-1 expressions of (P<0.05) and increased expressions of collagen-1 and TIMP-1 proteins and ECM content in the muscular tissues (P<0.05) without significant changes in the relative grip strength (P>0.05). Conclusion MMP-1/TIMP-1 imbalance in the skeletal muscle during aging affects ECM metabolism and leads to increased collagen fibers, which in turn affects the skeletal muscle mass and function and contribute to the onset of sarcopenia.