左归丸对激素性骨质疏松大鼠腰椎骨组织mTORC1 mRNA表达的影响

Effects of Zuogui Pill(左归丸) on the Expression of m TORC1 mRNA in Lumbar Vertebrae of Glucocorticoid-Induced Osteoporosis

目的探讨左归丸防治激素性骨质疏松的可能作用机制。方法 18只SD大鼠随机分为空白组、模型组、左归丸组,每组6只。模型组、左归丸组皮下注射地塞米松磷酸钠注射液0.6 mg/kg,每3天注射1次,构建激素性骨质疏松大鼠模型。左归丸组在造模第1天开始给予左归丸溶液1.9 g/(kg·d)灌胃,空白组、模型组给予生理盐水灌胃1 ml/(100 g·d),连续8周。检测大鼠腰椎骨密度、生物力学指标及腰椎骨组织Runt相关转录因子2(Runx2)、组织蛋白酶K(CTSK)和哺乳动物雷帕霉素靶蛋白复合物1(m TORC1)mRNA表达,HE染色观察腰椎形态学改变,检测大鼠血清碱性磷酸酶(AKP)活性。结果HE染色显示,模型组骨小梁内骨细胞数量减少,骨小梁表面成骨细胞及破骨细胞稀疏;与模型组比较,左归丸组骨小梁内骨细胞数量、骨小梁表面成骨细胞及破骨细胞明显增多。与空白组比较,模型组大鼠骨密度、骨矿物质含量、压缩强度、能量吸收值、m TORC1 mRNA表达及血清AKP活性降低(P<0.05);而左归丸组大鼠腰椎骨密度、骨矿物质含量、压缩强度、m TORC1 mRNA表达及血清AKP活性水平高于模型组(P<0.05)。结论左归丸能有效改善激素性骨质疏松,m TORC1可能是其重要靶点。

Objective To explore the possible action mechanism of Zuogui Pill（左 归丸） in prevention and treatment of glucocorticoid-induced osteoporosis（GIOP）. Methods A total of 18 SD rats were randomly divided into control group,model group and Zuogui Pill group,with 6 in each group. Rats in the model group and Zuogui Pill group received subcutaneous injection of dexamethasone,0. 6 mg/kg,1 time every 3 days,to establish GIOP rats model. Zuogui Pill group also received intragastrical administration of aqueous extract from Zuogui Pills,1. 9 g/（kg·d）.The control group and model group were given intragastrical administration of normal saline 1 ml/（100 g·d） for continuous 8 weeks. The bone mineral density,biomechanical index and the expression of Runt 2,cathepsin K（CTSK）and mammalian target of rapamycin complex 1（m TORC1） mRNA in lumbar vertebrae were detected. HE staining was used to observe the morphological changes of the lumbar spine. The serum alkaline phosphatase（AKP） activity in rats was detected. Results HE staining showed that the number of bone cells in the trabecular bone of the model group was reduced,and the osteoblasts and osteoclasts on the trabecular bone surface were sparse. Compared with the model group,the number of bone cells in the trabecular bone,osteoblasts and osteoclasts on the trabecular bone surface of the Zuogui Pill group were increased significantly. Compared with the control group,the bone density,bone mineral content,compressive strength,energy absorption,m TORC1 mRNA expression and serum AKP activity of the model group were decreased（P〈0. 05）. The lumbar vertebrae bone density,bone mineral content,compressive strength,m TORC1 mRNA expression and serum AKP activity of Zuogui Pill group were higher than those in the model group（P〈0. 05）. Conclusion Zuogui Pill can improve GIOP,and m TORC1 may be an important target.