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红景天苷治疗绝经后骨质疏松模型大鼠的效果及对谷胱甘肽过氧化物酶4表达的影响
毕文秀,王蓬,田爱现,杨宏伟
0
天津市天津医院检验科天津 300211;天津市天津医院骨科研究所天津 300211
摘要:
目的:探究红景天苷对绝经后骨质疏松模型大鼠的骨保护作用及其对谷胱甘肽过氧化物酶4(GPX4)表达的影响。方法:将18只SD雌性大鼠随机分为3组,每组6只:假手术组、模型组、红景天苷组,假手术组:行假手术处理,模型组:行大鼠双侧卵巢摘除,建立绝经后骨质疏松大鼠模型,红景天苷组:模型成功后,给予大鼠红景天苷水溶液(40 mg/kg)腹腔注射,模型组给予同等体积的生理盐水腹腔注射,每天1次,连续治疗2个月后,大鼠行双能X射线骨密度仪(DXA)拍摄,取大鼠血清行ELISA检测其骨钙素(OC)、I型前胶原氨基端前肽(PINP)、Ⅰ型胶原羧基末端肽(β-CTX)及4-羟基壬烯醛(4-HNE)水平,取大鼠股骨组织,行Micro-CT、Western blot、qRT-PCR、免疫组化检测。结果:DXA结果显示,较假手术组,模型组大鼠BMD明显降低,证明造模成功;治疗2个月后,红景天苷组的BMD较模型组明显升高(P <0.01)。Micro-CT结果显示,红景天苷组骨体积分数(BV/TV),骨小梁厚度(Tb.Th)及骨小梁数目(Tb.N)较模型组回升,骨小梁间距(Tb.Sp)降低(P <0.05)。ELISA结果表明,与假手术组比较,模型组OC、PINP水平降低,β-CTX、4-HNE升高,红景天苷组OC、PINP水平较模型组升高,β-CTX、4-HNE水平降低(P <0.01)。qRT-PCR和Western blot显示,模型组GPX4表达水平降低,红景天苷组GPX4表达水平比模型组明显升高。免疫组化显示,与假手术组比较,模型组GPX4蛋白表达水平明显降低,红景天苷组GPX4蛋白表达水平较模型组明显升高(P <0.01)。结论:红景天苷通过调控GPX4的表达水平抑制铁死亡进程,能有效治疗大鼠绝经后骨质疏松,提升骨量,改善其骨质疏松情况。
关键词:  红景天苷  绝经后骨质疏松  铁死亡  谷胱甘肽过氧化物酶4  骨形成
DOI:10.3969/j.issn.1007-6948.2025.05.026
投稿时间:2024-12-06
基金项目:国家自然科学基金青年项目(82304976);国家重点研发计划项目(2022YFC3601900)
Efficacy of Salidroside in treating postmenopausal osteoporosis in rats and analysis of glutathione peroxidase 4 expression
BI Wen-xiu,WANG Peng,TIAN Ai-xian
Abstract:
Objective To investigate the bone-protective effects of Salidroside on postmenopausal osteoporosis model rats and its influence on glutathione peroxidase 4 (GPX4) expression. Methods A total of 18 female SD rats were randomly divided into three groups, with six rats in each group. The groups were the sham-operated group, the model group, and the Salidroside group. The sham surgery group underwent sham operation, while the model group underwent bilateral ovariectomy to establish a postmenopausal osteoporosis rat model. Salidroside group: After successful modeling, rats were administered Salidroside solution (40 mg/kg) via intraperitoneal injection, while the model group received an equal volume of physiological saline via intraperitoneal injection, once daily for two months. Subsequently, rats underwent DXA testing, serum samples were collected for ELISA testing, and femoral bone tissue was harvested for Micro-CT, Western blot, qRT-PCR, and immunohistochemical analysis. Results DXA results showed that compared with the sham-operated group, BMD in the model group was significantly reduced, confirming the success of the model. After drug administration, BMD in the Salidroside group was significantly higher than that in the model group (P <0.01). Micro-CT results showed that the red ginseng glycoside group had significantly higher BV/TV, Tb.Th, and Tb.N compared to the model group, while Tb.Sp was significantly lower (P <0.05). ELISA results indicated that compared with the sham-operated group, serum osteocalcin (OC) and type I procollagen N-terminal propeptide (PINP) levels were significantly reduced in the model group, while type I collagen C-terminal propeptide (β-CTX) levels were significantly increased, and 4-hydroxy-2-nonenal (4-HNE) levels were significantly elevated. The Salidroside group showed significantly higher levels of OC and PINP compared to the model group, while β-CTX and 4-HNE expression levels were significantly lower (P <0.01). qRT-PCR and Western blot analysis showed that GPX4 expression levels were reduced in the model group, while the Salidroside group exhibited significantly higher GPX4 expression levels compared to the model group. Immunohistochemistry showed that compared with the sham-operated group, the GPX4 protein expression levels in the model group were significantly reduced, while those in the Salidroside group were significantly increased compared with the model group (P <0.01). Conclusion Salidroside inhibits the ferroptosis process by regulating the expression levels of GPX4, effectively treating postmenopausal osteoporosis in rats, increasing bone mass, and improving their osteoporosis condition.
Key words:  Salidroside  postmenopausal osteoporosis  ferroptosis  glutathione peroxidase 4  bone formation

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