张伟, 张军敏, 张富强, 王天一, 韩冠英. 黄原胶对前交叉韧带切断术所致骨关节炎的疗效及其机制J. 药学学报, 2017,52(10): 1533-1540. doi: 10.16438/j.0513-4870.2017-0319
引用本文: 张伟, 张军敏, 张富强, 王天一, 韩冠英. 黄原胶对前交叉韧带切断术所致骨关节炎的疗效及其机制J. 药学学报, 2017,52(10): 1533-1540. doi: 10.16438/j.0513-4870.2017-0319
ZHANG Wei, ZHANG Jun-min, ZHANG Fu-qiang, WANG Tian-yi, HAN Guan-ying. Effect and mechanism of xanthan gum on osteoarthritis caused by anterior cruciate ligament transectionJ. Acta Pharmaceutica Sinica, 2017,52(10): 1533-1540. doi: 10.16438/j.0513-4870.2017-0319
Citation: ZHANG Wei, ZHANG Jun-min, ZHANG Fu-qiang, WANG Tian-yi, HAN Guan-ying. Effect and mechanism of xanthan gum on osteoarthritis caused by anterior cruciate ligament transectionJ. Acta Pharmaceutica Sinica, 2017,52(10): 1533-1540. doi: 10.16438/j.0513-4870.2017-0319

黄原胶对前交叉韧带切断术所致骨关节炎的疗效及其机制

Effect and mechanism of xanthan gum on osteoarthritis caused by anterior cruciate ligament transection

  • 摘要: 本研究评价黄原胶(xanthan gum,XG)对前交叉韧带切断术(anterior cruciate ligament transaction,ACLT)所致的兔膝关节骨关节炎(osteoarthritis,OA)模型中软骨损伤的保护作用,并探讨XG对OA软骨中caspase-3、Bax蛋白表达的影响。将60只雄性新西兰大耳白兔按随机数字表法分为6组,每组10只,随机选取1组为正常对照组(control组),剩余5组右膝采用ACLT建立OA模型,并根据药物干预不同分为模型组(model组)、XG-0.6 mg·kg-1、XG-1.2 mg·kg-1、XG-2.4 mg·kg-1治疗组和玻璃酸钠(sodium hyaluronate,SH-1.2 mg·kg-1)治疗组。测量治疗过程中各组兔膝关节局部温度和膝关节宽度;治疗结束后,对各组兔关节进行大体形态学观察;通过HE染色对各组兔关节软骨组织病理学形态进行观察;Western blot法检测各组家兔软骨细胞中Bax和caspase-3的激活态cleaved caspase-3含量。实验结果表明,XG可抑制OA所致的膝关节局部温度的上升和膝关节宽度的增加,且具有剂量依赖性;XG具有改善由OA所致的股骨髁和胫骨平台形态学异常和组织损伤的作用;Western blot结果表明:与control组相比,model组和XG-0.6 mg·kg-1组家兔膝关节软骨细胞中Bax和cleaved caspase-3水平显著增加(P<0.01),model组和XG-0.6 mg·kg-1组间兔膝关节软骨细胞中Bax和cleaved caspase-3水平无显著性差别(P>0.05),且明显高于XG-1.2 mg·kg-1和XG-2.4 mg·kg-1组(P<0.01),XG-2.4 mg·kg-1和XG-1.2 mg·kg-1组间兔骨关节软骨细胞中cleaved caspase-3水平无显著性差别(P>0.05),XG-2.4 mg·kg-1组兔骨关节软骨细胞中Bax水平低于XG-1.2 mg·kg-1组(P<0.05)。综上所述,XG能够有效地保护OA中的软骨损伤,并能够抑制OA软骨中Bax和caspase-3蛋白的表达。

     

    Abstract: The study is designed to evaluate the protective effect of xanthan gum (XG) injection on cartilage injury in the rabbit osteoarthritis (OA) model induced by anterior cruciate ligament transection (ACLT), and to explore the effect of XG on the expression of caspase-3 and Bax protein in OA cartilage. Sixty male New Zealand white rabbits were randomly divided into 6 groups (n=10) according to random number table method, and one group was selected randomly as the normal control group (control) while the other 5 groups of right knee were used to establish the OA model with ACLT, which were then divided into model group (model), XG-0.6 mg·kg-1, XG-1.2 mg·kg-1, XG-2.4 mg·kg-1 treatment group and sodium hyaluronate (SH-1.2 mg·kg-1) treatment group according to drug intervention. The knee joint temperature and knee joint width of each group were measured in the course of treatment. After treatment, the macroscopic morphology of rabbit joints in each group was observed. The pathological morphology of articular cartilage of rabbits in each group was observed using HE staining. The expression of Bax and cleaved caspase-3 in the cartilage of rabbits were detected by Western blot. The result shows that XG inhibited the increase in knee joint temperature and knee width caused by OA in a dose-dependent manner. XG improved the morphological abnormalities and tissue injuries of the femoral condyle and tibial plateau caused by OA. Western blot result shows that, compared with the control group, the levels of Bax and cleaved caspase-3 in knee cartilage cells of model group and XG-0.6 mg·kg-1 group were significantly increased (P<0.01). However, no significant difference was observed in the levels of Bax and cleaved caspase-3 between the model group and the XG-0.6 mg·kg-1 group (P>0.05). These two groups are significantly higher than those of XG-1.2 mg·kg-1 and XG-2.4 mg·kg-1 (P<0.01) groups. Meanwhile, no significant difference was observed in the level of cleaved caspase-3 between the knee cartilage in XG-2.4 mg·kg-1 and XG-1.2 mg·kg-1 group (P>0.05). The level of Bax in knee cartilage in XG-2.4 mg·kg-1 group was lower than that of XG-1.2 mg·kg-1 group (P<0.05). In conclusion, XG effectively protected cartilage damage in OA, and inhibited the expression of Bax and caspase-3 protein in OA cartilage.

     

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