摘要
目的评价龟鹿二仙胶对去势大鼠骨质疏松的保护作用并探讨其机制。方法120只大鼠,随机分为正常组,模型组,龟鹿二仙胶低、中、高剂量组和阿法骨化醇组,共6组,除正常组外均去势造模。龟鹿二仙胶按低、中、高剂量(0.5,1.5,2.5 g·kg^(-1)·d^(-1)),阿法骨化醇按0.1μg·kg^(-1)·d^(-1)分别灌胃干预,正常组和模型组分别给予等量生理盐水。采用HE染色检测大鼠股骨病理改变,采用试剂盒检测股骨钙(calcium,Ca)、磷(phosphorus,P)、羟脯氨酸(hydroxyproline,Hyp)、碱性磷酸酶(alkaline phosphatase,ALP)和抗酒石酸酸性磷酸酶(tartrate-resistant acid phosphatase,TRAP),同时采用蛋白质印迹法检测去势大鼠股骨TGF-β、p-Smad-3蛋白的表达以及p-JNK、p-ERK、p-P38、p-NF-κB P65蛋白的表达。结果与正常组比较,模型组大鼠股骨Ca、P、Hyp、ALP水平显著下降(P<0.01),TRAP水平显著升高(P<0.01),骨小梁结构排列紊乱、形态变薄且有断裂迹象,TGF-β、p-Smad-3蛋白表达水平下调以及p-JNK、p-ERK、p-P38与p-NF-κB P65蛋白表达水平上调(P<0.01)。与模型组比较,龟鹿二仙胶显著增加大鼠股骨Ca、P、Hyp、ALP水平(P<0.01),降低股骨中TRAP水平(P<0.01),改善股骨病理改变,同时龟鹿二仙胶显著诱导TGF-β、p-Smad-3蛋白表达并显著降低p-JNK、p-ERK、p-P38与p-NF-κB P65蛋白表达(P<0.01)。结论龟鹿二仙胶能显著改善去势大鼠的骨质疏松,其机制与激活TGF-β/Smad信号通路和抑制MAPK/NF-κB信号通路有关。
OBJECTIVE To evaluate the protective effect of Guilu Erxian Jiao on osteoporosis in ovariectomized rats and to explore its mechanism.METHODS A total of 120 rats were randomly divided into normal group,model group,low-dose,medium-dose and high-dose of Guilu Erxian Jiao group and alfacalcidol group.There were 6 groups in total,and all of them were emasculated and modeled except the normal group.Guilu Erxian Jiao was administrated with low,medium,high dose(0.5,1.5,2.5 g·kg^(-1)·d^(-1)),alfacalcidol was administrated with 0.1μg·kg^(-1)·d^(-1)dose,the normal group and the model group were given the same amount of normal saline respectively.The pathological changes of femur in rats were detected by HE staining,and the calcium(Ca),phosphorus(P),hydroxyproline(Hyp),alkaline phosphatase(ALP)and tartrate-resistant acid phosphatase(TRAP)of femur were detected by kits.At the same time,Western blotting was used to detect the expression of TGF-β,p-Smad-3 protein and p-JNK,p-ERK,p-P38,p-NF-κB P65 protein in femur of ovariectomized rats.RESULTS Compared with the normal group,the levels of Ca,P,Hyp and ALP in femur of rats in the model group were significantly decreased(P<0.01),while the level of TRAP was significantly increased(P<0.01).The trabecular structure of rats in the model group was disordered,the morphology was thinned and showed signs of fracture.The protein expression levels of TGF-βand p-Smad-3 in femur of the model group were down-regulated,while the protein expression levels of p-JNK,p-ERK,p-P38 and p-NF-κBP65 in femur were up-regulated(P<0.01).Compared with the model group,Guilu Erxian Jiao significantly increased the levels of Ca,P,Hyp and ALP in femur of rats(P<0.01),decreased the level of TRAP in femur of rats(P<0.01),and improved the pathological changes of femur.Meanwhile,Guilu Erxian Jiao significantly induced the expression of TGF-βand p-Smad-3 protein,and significantly decreased the expression of p-JNK,p-ERK,p-P38 and p-NF-κBP65 protein(P<0.01).CONCLUSION Guilu Erxian Jiao can significantly improve osteoporosis in ovariectomized rats,and the mechanism is related to the activation of TGF-β/Smad signaling pathway and the inhibition of MAPK/NF-κB signaling pathway.
作者
徐卫峰
朱旭祥
何丹
王善付
尹恒
XU Weifeng;ZHU Xuxiang;HE Dan;WANG Shanfu;YIN Heng(Wuxi Affiliated Hospital of Nanjing University of Chinese Medicine,Wuxi 214071,China)
出处
《中国现代应用药学》
CAS
CSCD
北大核心
2022年第13期1661-1667,共7页
Chinese Journal of Modern Applied Pharmacy
基金
国家自然科学基金项目(81973878)
江苏省自然科学基金项目(BK20180167)
无锡市卫生计生委科研项目(Q201628)
