槲皮素通过改善肠黏膜屏障功能治疗去势骨质疏松大鼠模型的骨量丢失OA
Quercetin Ameliorates Bone Loss in Ovariectomized Osteoporotic Rats by Improving Intestinal Mucosal Barrier Function
目的:基于对肠黏膜屏障的保护作用探究槲皮素治疗去势骨质疏松大鼠骨量丢失的作用机制.方法:将30只成年雌性大鼠随机分为假手术组、模型组、槲皮素组,每组各10只.通过常规背部双切口去卵巢术建立骨质疏松大鼠模型,造模12周后槲皮素组给予槲皮素灌胃干预,其余组给予等量生理盐水灌胃.干预12周后分别通过微计算机断层扫描技术(Micro-CT)检测各组大鼠骨组织的骨密度(BMD)、骨体积分数(BV/TV)、骨小梁数目(Tb.N)、骨小梁厚度(Tb.Th)、骨小梁间隙(Tb.Sp)、骨小梁骨形态因子(Tb.Pf)等骨微结构参数;苏木精-伊红(HE)染色检测各组大鼠骨组织及结肠组织的病理形态变化;三点弯曲试验检测各组大鼠股骨最大载荷;酶联免疫吸附试验检测各组大鼠血清中的D-乳酸(D-LAC)、白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)、Ⅰ型胶原交联C-末端肽(CTX-1)、抗酒石酸酸性磷酸酶5b(TRAcP-5b)、脂多糖(LPS)的含量;蛋白质印迹法检测结肠组织闭锁小带蛋白1(ZO-1)、闭合蛋白(Occludin)的蛋白表达水平.结果:与假手术组比较,模型组骨组织骨密度、Tb.N、BV/TV、Tb.Th、股骨最大载荷、结肠组织ZO-1、闭合蛋白表达水平均显著降低,差异有统计学意义(P＜0.05),而骨组织 Tb.Sp、Tb.Pf 及血清中 D-LAC、LPS、IL-1β、TNF-α、TRAcP-5b 和 CTX-1 含量显著升高,差异有统计学意义(P＜0.05).与模型组比较,槲皮素组骨组织骨密度、Tb.N、BV/TV、Tb.Th、股骨最大载荷、结肠组织ZO-1、闭合蛋白表达水平显著升高,差异有统计学意义(P＜0.05)、而骨组织Tb.Sp、Tb.Pf及血清中D-LAC、LPS、IL-1β、TNF-α、TRAcP-5b和CTX-1含量显著降低,差异有统计学意义(P＜0.05).结论:槲皮素能缓解去势骨质疏松大鼠模型的骨量丢失,改善骨质疏松,其作用机制可能与改善肠道黏膜的屏障作用有关.
Objective:To explore the mechanism underlying the therapeutic effect of quercetin on bone loss in ovariectomized osteoporotic rats,based on its protective role in the intestinal mucosal barrier.Methods:Thirty adult female rats were randomly divided into three groups of 10 rats each:the sham-operated group,the model group,and the quercetin group.The osteoporotic rat model was established via bilateral ovariectomy through routine double dorsal inci-sions.Twelve weeks after modeling,the quercetin group was administered quercetin by gavage,while the other groups received an equal volume of normal saline by gavage.After 12 weeks of intervention,the following assessments were per-formed:micro-computed tomography(micro-CT)was used to assess bone microstructural parameters in rat bone tissues,including bone mineral density(BMD),bone volume/tissue volume(BV/TV),trabecular number(Tb.N),trabecular thickness(Tb.Th),trabecular separation(Tb.Sp),and trabecular pattern factor(Tb.Pf).Hematoxylin-eosin(HE)stai-ning was conducted to observe the pathological morphological changes of bone and colon tissues in each group.A three-point bending test was performed to measure the maximum femoral load in rats.Enzyme-linked immunosorbent assay(ELISA)was employed to determine the serum levels of D-lactic acid(D-LAC),interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),C-terminal telopeptide of type Ⅰ collagen(CTX-1),tartrate-resistant acid phosphatase 5b(TRAcP-5b),and lipopolysaccharide(LPS).Western blot analysis was used to detect the protein expression levels of zonula occludens-1(ZO-1)and occludin in colon tissues.Results:Compared with the sham-operated group,the model group exhibited sig-nificant decreases in bone tissue BMD,Tb.N,BV/TV,Tb.Th,and maximum femoral load,as well as in the protein expression levels of ZO-1 and occludin in colon tissues(P＜0.05).Meanwhile,Tb.Sp,Tb.Pf in bone tissue,and serum levels of D-LAC,LPS,IL-1β,TNF-α,TRAcP-5b,and CTX-1 were significantly elevated in the model group(P＜0.05).Compared with the model group,the quercetin group showed significant increases in bone tissue BMD,Tb.N,BV/TV,Tb.Th,and maximum femoral load,as well as in the protein expression levels of ZO-1 and occludin in colon tissue(P＜0.05).In con-trast,Tb.Sp,Tb.Pf in bone tissue,and serum concentrations of D-LAC,LPS,IL-1β,TNF-α,TRAcP-5b,and CTX-1 were signifi-cantly reduced in the quercetin group(P＜0.05).Conclusion:Quercetin can alleviate bone loss and ameliorate osteoporosis in ovariectomized osteoporotic rats,and its mechanism may be related to the improvement of intestinal mucosal barrier function.
丰瑞兵;王晴;王威;熊自仁;刘曦明
中国人民解放军中部战区总医院(武汉,430070)||湖北省中医院武汉体育学院运动医学院中国人民解放军中部战区总医院(武汉,430070)||湖北省中医院武汉科技大学医学院中国人民解放军中部战区总医院(武汉,430070)
医药卫生
槲皮素骨质疏松症肠黏膜屏障骨量丢失
quercetinosteoporosisintestinal mucosal barrierbone loss
《中国中医骨伤科杂志》 2026 (10)
18-24,7
中部战区总医院博士后科研项目(96021)湖北省卫生健康委员会转化医学项目(WJ2021ZH0010)武汉市2023年度知识创新专项(2023020201010179)
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