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目的:研究淫羊藿女贞子水煎剂及其有效成分提取物防治维甲酸(RA)致大鼠骨质疏松症(OP)的作用机制。方法:SPF级雄性Wistar大鼠36只,随机分为6组,即正常组、模型组、淫羊藿-女贞子水煎剂组、淫羊藿-女贞子提取物低、中、高剂量组,RA(70 mg·kg-1)ig造模,造模的同时给药,给药组分别给予淫羊藿-女贞子水煎剂(9.5 g·kg-1)及药对有效成分提取物低、中、高3个剂量(50,100,200 mg·kg-1)ig治疗2周,免疫组化法检测骨组织中凋亡相关因子B细胞淋巴瘤/白血病-2(Bcl-2),p53的蛋白表达;实时RT-q PCR法检测骨组织中转化生长因子-β1(TGF-β1),果蝇MAD类似基因2(Smad2),Smad3,Smad7 mRNA的表达。结果:与正常组比较,模型组大鼠骨组织Bcl-2蛋白表达明显降低,而p53蛋白表达显著升高,骨组织TGF-β1及Smad2,Smad3 mRNA相对表达量均明显下降,Smad7 mRNA相对表达量明显升高,均具有统计学差异(P<0.05,P<0.01);与模型组比较,各给药组可不同程度上调Bcl-2以及TGF-β1,Smad2,Smad3的表达水平,下调p53,Smad7的表达水平,均具有明显统计学差异(P<0.05,P<0.01)。结论:淫羊藿-女贞子抗OP的作用机制可能与其维持凋亡与抗凋亡间的平衡,抑制骨组织细胞凋亡以及调控TGF-β/Smads通路信号转导有关。
Objective: To study the mechanism of action of Epimedium Ligustrum lucidum decoction and its active ingredient extract in prevention and treatment of rat osteoporosis (OP) induced by retinoic acid (RA). Methods: Thirty-six male Sprague-Dawley rats were randomly divided into 6 groups: normal group, model group, Epimedium-Ligustrum lucidum decoction group, Epimedium-Ligustrum lucidum extract low, medium and high Dose group, RA (70 mg · kg-1) ig model, at the same time the model of administration, the administration group were given Epimedium - Ligustrum lucidum decoction (9.5 g · kg-1) The extracts were treated with low, medium and high doses of ig (50,100,200 mg · kg-1) ig for 2 weeks. The expression of Bcl-2 and Bcl-2 in bone tissue were detected by immunohistochemistry. The expression of TGF-β1, Smad2, Smad3 and Smad7 in bone tissue were detected by real-time RT-q PCR. Results: Compared with the normal group, the expression of Bcl-2 protein and the expression of p53 protein in the model group were significantly decreased, while the relative expression of TGF-β1, Smad2 and Smad3 mRNA in the model group were significantly decreased (P <0.05, P <0.01). Compared with the model group, the expression levels of Bcl-2, TGF-β1, Smad2 and Smad3 were up-regulated , Smad7 expression levels were significantly different (P <0.05, P <0.01). CONCLUSION: The mechanism of anti-opioid effect of Epimedium-Ligustrum lucidum may be related to maintaining the balance between apoptosis and anti-apoptosis, inhibiting the apoptosis of bone tissue and regulating the signal transduction of TGF-β / Smads pathway.