GYY4137通过提高自噬水平和降低氧化应激来保护老年雌性大鼠骨量流失

GYY4137 protects bone loss in elderly female rats by increasing autophagy levels and reducing oxidative stress

目的观察GYY4137对老年大鼠骨量影响以及对氧化应激水平和自噬水平的影响。方法10只年轻大鼠和20只老年雌性Sprague-Dawley大鼠随机分为3组,对照组(Con,10只年轻大鼠)、模型组(Mod,10只老年大鼠)和治疗组(Tre,10只老年大鼠),每组10只。在实验过程中,治疗组接受GYY4137治疗。治疗12周后,检测血清氧化应激指标水平。治疗12周后使用影像学和组织学评估股骨骨量改变以及蛋白印迹(WB)检测自噬信号通路关键蛋白的改变。结果治疗12周后,与Mod组相比,Tre组大鼠血清MDA和ROS水平明显降低,GSH和SOD水平明显升高,组间差异有统计学意义(P<0.05);和Mod组相比,Micro-CT和组织学评估显示治疗组的骨小梁数量较多,具有较高的骨密度(BMD)、骨体积/总体积(BV/TV)、骨小梁厚度(Tb.Th)及骨小梁数目(Tb.N),和较低的骨小梁分离度(Tb.Sp),差异比较有统计学意义(P均<0.05)。WB检测结果显示H2S治疗后Atg 5,LC3和Beclin1表达明显高于对照组(P<0.05);而p62显著低于对照组(P<0.05)。结论GYY4137可以通过提高老年大鼠自噬水平和降低氧化应激来提高老年大鼠骨量和骨密度。

Objective To observe the effect of GYY4137 on bone mass and bone mineral density(BMD) and autophagy in aged rats.Methods Ten young rats and twenty old female Sprague-Dawley rats were randomly divided into three groups:control group(Con,10 young rats),model group(Mod,10 old rats),and treatment group(Tre,10 old rats),with 10 rats in each group.During the experiment,rats in the treatment group received GYY4137 treatment.After 12 weeks of treatment,serum oxidative stress indicators were measured.After 12 weeks,bone mass change was assessed using imaging and histology.Changes of key proteins in the autophagy signaling pathway were detected using Western blotting(WB).Results Compared with those in the Mod group,the serum MDA and ROS levels reduced significantly in the Tre group,and the GSH and SOD levels increased significantly after 12 weeks.The differences between the groups were statistically significant(P<0.05).Compared with those in the Mod group,there were more bone trabeculae,higher BMD,bone volume/total volume(BV/TV),trabecular thickness(Tb.Th),and the number of trabecular bones(Tb.N),and lower trabecular bone separation(Tb.Sp) in the treatment group,as evaluated with micro-CT and histology.The difference was statistically significant(all P<0.05).WB test result showed that the expression of Atg 5,LC3,and Beclinl after H2 S treatment was significantly higher than that in the control group(P<0.05),while p62 was significantly lower than that in the control group(P<0.05).Conclusion GYY4137 increases bone mass and BMD by increasing the level of autophagy and reducing the oxidative stress in aged rats.