Chinese Journal of Tissue Engineering Research ›› 2025, Vol. 29 ›› Issue (5): 888-898.doi: 10.12307/2024.593
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Lan Shuangli1, Xiang Feifan2, Deng Guanghui2, Xiao Yukun2, Yang Yunkang2, Liang Jie2
Received:
2023-08-04
Accepted:
2023-12-14
Online:
2025-02-18
Published:
2024-06-01
Contact:
Liang Jie, Master, Attending physician, Department of Bone and Joint Surgery, Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China
About author:
Lan Shuangli, Department of Hepatobiliary Surgery, Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China
Supported by:
CLC Number:
Lan Shuangli, Xiang Feifan, Deng Guanghui, Xiao Yukun, Yang Yunkang, Liang Jie. Naringin inhibits iron deposition and cell apoptosis in bone tissue of osteoporotic rats [J]. Chinese Journal of Tissue Engineering Research, 2025, 29(5): 888-898.
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2.1 各组大鼠造模结果及一般表现 在实验过程中未发生动物死亡的现象。造模后,假手术组大鼠活泼活动,反应机敏,皮毛顺滑浓密,摄食、饮水及睡眠未见异常;骨质疏松组大鼠精神状态偏于狂躁不安,反应迟钝,皮毛暗淡稀疏,大鼠在实验过程中往往处于少动嗜睡的状态,摄食与饮水意愿不强烈;柚皮苷低剂量组、柚皮苷高剂量组、柚皮苷高剂量+DKK-1组大鼠的情绪、精神状态较为稳定,反应较为敏捷,皮毛较为顺整。 与假手术组相比,骨质疏松组大鼠血清钙水平和骨密度明显下降(P < 0.05),血清骨钙素和磷的水平明显升高(P < 0.05),证实造模成功。 2.2 各组大鼠血清中骨钙素、钙、磷水平及骨密度的变化 与假手术组相比,骨质疏松组、柚皮苷低剂量组、柚皮苷高剂量组、柚皮苷高剂量+DKK-1组大鼠血清钙水平和骨密度下降(P < 0.05),骨钙素和磷水平升高(P < 0.05);与骨质疏松组相比,柚皮苷干预组大鼠血清钙水平和骨密度升高(P < 0.05),骨钙素和磷水平下降(P < 0.05);与柚皮苷高剂量组相比,柚皮苷低剂量组、柚皮苷高剂量+DKK-1组大鼠血清钙水平和骨密度下降(P < 0.05),骨钙素和磷水平升高(P < 0.05),见图1。 2.3 各组大鼠骨微结构的变化 Micro-CT扫描结果显示,与假手术组相比,骨质疏松组、柚皮苷低剂量组、柚皮苷高剂量组、柚皮苷高剂量+DKK-1组大鼠胫骨组织的平均骨体积分数和平均骨小梁数下降(P < 0.05),骨小梁间距升高(P < 0.05);与骨质疏松组相比,柚皮苷干预组大鼠胫骨组织的平均骨体积分数和平均骨小梁数升高(P < 0.05),骨小梁间距下降(P < 0.05);与柚皮苷高剂量组相比,柚皮苷低剂量组、柚皮苷高剂量+DKK-1组大鼠胫骨组织的平均骨体积分数和平均骨小梁数下降(P < 0.05),骨小梁间距升高(P < 0.05),见图2。 2.4 各组大鼠骨组织病理损伤 苏木精-伊红染色结果显示,假手术组大鼠胫骨组织形态正常,结构完整,骨小梁粗细匀称,排列致密有序,骨小梁内纹理清晰可辨,骨皮质厚度均一,未见明显异常;骨质疏松组大鼠胫骨组织结构破坏明显,骨小梁数量减少,排列紊乱,结构变细,模糊不清晰,部分有断裂、缺失现象,髓腔扩张明显,骨皮质变薄,出现部分空洞结构;与骨质疏松组相比,柚皮苷低剂量组、柚皮苷高剂量组、柚皮苷高剂量+DKK-1组大鼠胫骨组织病理症状明显改善,骨小梁结构宽度接近正常,排列较为规则,骨皮质明显增厚,尤以柚皮苷低剂量组、柚皮苷高剂量组改善程度最为明显,见图3。 2.5 各组大鼠胫骨组织细胞凋亡情况 胫骨组织TUNEL染色显示,与假手术组相比,骨质疏松组、柚皮苷低剂量组、柚皮苷高剂量组、柚皮苷高剂量+DKK-1组细胞凋亡率升高(P < 0.05);与骨质疏松组相比,柚皮苷低剂量组、柚皮苷高剂量组、柚皮苷高剂量+DKK-1组细胞凋亡率下降(P < 0.05);与柚皮苷高剂量组相比,柚皮苷低剂量组、柚皮苷高剂量+DKK-1组细胞凋亡率升高(P < 0.05),见图4。 2.6 各组大鼠胫骨组织中相关基因的表达 胫骨组织PCR检测显示,与假手术组相比,骨质疏松组、柚皮苷低剂量组、柚皮苷高剂量组、柚皮苷高剂量+DKK-1组抗酒石酸酸性磷酸酶、铁吸收相关蛋白受体1、Bax的mRNA表达升高(P < 0.05),碱性磷酸酶、膜铁转运蛋白1、Bcl-2、Wnt1、β-catenin的mRNA表达降低(P < 0.05);与骨质疏松组相比,柚皮苷低剂量组、柚皮苷高剂量组、柚皮苷高剂量+DKK-1组抗酒石酸酸性磷酸酶、铁吸收相关蛋白受体1、Bax的mRNA表达降低(P < 0.05),碱性磷酸酶、膜铁转运蛋白1、Bcl-2、Wnt1、β-catenin的mRNA表达升高(P < 0.05);与柚皮苷高剂量组相比,柚皮苷低剂量组、柚皮苷高剂量+DKK-1组抗酒石酸酸性磷酸酶、铁吸收相关蛋白受体1、Bax的mRNA表达升高(P < 0.05),碱性磷酸酶、膜铁转运蛋白1、Bcl-2、Wnt1、β-catenin的mRNA表达降低(P < 0.05),见图5。 2.7 各组大鼠胫骨组织中氧化应激水平 胫骨组织超氧化物阴离子二氢乙啶染色显示,与假手术组相比,骨质疏松组、柚皮苷低剂量组、柚皮苷高剂量组、柚皮苷高剂量+DKK-1组大鼠活性氧含量升高(P < 0.05);与骨质疏松组相比,柚皮苷低剂量组、柚皮苷高剂量组、柚皮苷高剂量+DKK-1组活性氧含量降低(P < 0.05);与柚皮苷高剂量组相比,柚皮苷低剂量组、柚皮苷高剂量+DKK-1组活性氧含量升高(P < 0.05),见图6。 与假手术组相比,骨质疏松组、柚皮苷低剂量组、柚皮苷高剂量组、柚皮苷高剂量+DKK-1组大鼠血清丙二醛水平升高(P < 0.05),超氧化物歧化酶水平下降(P < 0.05);与骨质疏松组相比,柚皮苷低剂量组、柚皮苷高剂量组、柚皮苷高剂量+DKK-1组大鼠血清丙二醛水平下降(P < 0.05),超氧化物歧化酶水平升高(P < 0.05);与柚皮苷高剂量组相比,柚皮苷低剂量组、柚皮苷高剂量+DKK-1组大鼠血清丙二醛水平明显升高(P < 0.05),超氧化物歧化酶水平下降(P < 0.05),见图7。 2.8 各组大鼠胫骨组织和肝组织中铁沉积情况 普鲁士蓝染色显示,与假手术组相比,骨质疏松组、柚皮苷低剂量组、柚皮苷高剂量组、柚皮苷高剂量+DKK-1组大鼠肝组织与骨组织中普鲁士蓝阳性细胞比例升高(P < 0.05);与骨质疏松组相比,柚皮苷低剂量组、柚皮苷高剂量组、柚皮苷高剂量+DKK-1组大鼠肝组织与骨组织中中普鲁士蓝阳性细胞的比例降低(P < 0.05);与柚皮苷高剂量组相比,柚皮苷低剂量组、柚皮苷高剂量+DKK-1组大鼠肝组织与骨组织中普鲁士蓝阳性细胞比例升高(P < 0.05),见图8。 胫骨组织免疫组化染色显示,与假手术组相比,骨质疏松组、柚皮苷低剂量组、柚皮苷高剂量组、柚皮苷高剂量+DKK-1组膜铁转运蛋白1的表达降低(P < 0.05),铁吸收相关蛋白受体1的表达升高(P < 0.05);与骨质疏松组相比,柚皮苷低剂量组、柚皮苷高剂量组、柚皮苷高剂量+DKK-1组膜铁转运蛋白1的表达升高(P < 0.05),铁吸收相关蛋白受体1的表达降低(P < 0.05);与柚皮苷高剂量组相比,柚皮苷低剂量组、柚皮苷高剂量+DKK-1组膜铁转运蛋白1的表达降低(P < 0.05),铁吸收相关蛋白受体1的表达升高(P < 0.05),见图9。 2.9 各组大鼠胫骨组织中抗酒石酸酸性磷酸酶和碱性磷酸酶的表达 胫骨组织免疫荧光染色显示,与假手术组相比,骨质疏松组、柚皮苷低剂量组、柚皮苷高剂量组、柚皮苷高剂量+DKK-1组碱性磷酸酶表达明显降低(P < 0.05),抗酒石酸酸性磷酸酶表达升高(P < 0.05);与骨质疏松组相比,柚皮苷低剂量组、柚皮苷高剂量组、柚皮苷高剂量+DKK-1组碱性磷酸酶表达升高(P < 0.05),抗酒石酸酸性磷酸酶表达明显降低(P < 0.05);与柚皮苷高剂量组相比,柚皮苷低剂量组、柚皮苷高剂量+DKK-1组碱性磷酸酶表达降低(P < 0.05),抗酒石酸酸性磷酸酶表达升高(P < 0.05),见图10。 2.10 各组大鼠胫骨组织中Wnt1信号通路相关蛋白的表达 胫骨组织Western blot检测显示,与假手术组相比,骨质疏松组、柚皮苷低剂量组、柚皮苷高剂量组、柚皮苷高剂量+DKK-1组Bcl-2、Wnt1、β-catenin蛋白表达降"
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