【摘要】 目的 探讨竹节参皂苷Ⅳa对膝骨关节炎（KOA）的治疗作用及其作用机制。方法 将50只SD大鼠随机分为对照组、模型组（KOA模型）、低剂量实验组(建模后灌胃给予5 mg·kg^-1竹节参皂苷Ⅳa)、高剂量实验组(建模后灌胃给予15 mg·kg^-1竹节参皂苷Ⅳa)、阳性对照组(建模后灌胃给予0.27 g·kg^-1的仙灵骨葆胶囊),每组10只，连续给药8周。给药结束后检测各组大鼠关节肿胀度，并收集血样和软骨组织备用。用酶联免疫吸附试验（ELISA）法检测血清炎性因子相关指标水平，用蛋白质印迹法（Western blot）检测软骨组织蛋白表达水平，用免疫组化法检测各组大鼠软骨组织Toll样受体4（TLR4）表达水平。结果 对照组、模型组、高剂量实验组和阳性对照组大鼠8周关节肿胀度分别为（0.17±0.03）、（4.84±0.58）、（2.57±0.18）和（2.30±0.21） mm,白细胞介素-1β（IL-1β）表达水平分别为（3.67±0.17）、（16.09±0.88）、（7.26±0.65）和（6.86±0.40） pg·mL^-1,基质金属蛋白酶1（MMP-1）表达水平分别为（20.41±1.20）、（67.34±4.90）、（33.18±3.63）和（29.93±2.39） ng·mL^-1,TLR4蛋白表达水平分别为0.25±0.03、1.10±0.11、0.45±0.05和0.40±0.04,髓样分化因子88（MyD88）蛋白表达水平分别为0.36±0.04、0.92±0.10、0.43±0.05和0.61±0.06;以上指标，模型组与对照组比较，高剂量实验组、阳性对照组分别与模型组比较，低剂量实验组与高剂量组比较，差异均具有统计学意义（均P<0.05）。结论 竹节参皂苷Ⅳa可抑制炎性反应和软骨细胞凋亡改善KOA大鼠关节肿胀，这与抑制TLR4/MyD88信号通路有关。更多还原

【Abstract】 Objective To investigate the therapeutic effect and mechanism of chikusetsusaponin Ⅳa on knee osteoarthritis（KOA）. Methods Fifty SD rats were randomly divided into control group, model group（KOA model）, experimental-L group(5 mg·kg^-1 chikusetsusaponin Ⅳa after modeling), experimental-H group(15 mg·kg^-1 chikusetsusaponin Ⅳa after modeling) and positive control group(0.27 g·kg^-1 Xianling Gubao capsule after modeling), 10 in each group, were given continuous administration for 8 weeks. The degree of joint swelling of rats in each group was detected after administration, and blood samples and cartilage tissues were collected for use. Serum inflammatory factor related indexes were detected by enzyme linked immunosorbent assay（ELISA）, cartilage tissue protein expression levels were detected by Western blot, and Toll-like receptor 4（TLR4） expression levels were detected by immunohistochemistry. Results The joint swelling of control group,model group,experimental-H group and positive control group at 8 weeks were（ 0. 17 ± 0. 03）,（ 4. 84 ± 0. 58）,（ 2. 57 ± 0. 18）and（ 2. 30 ± 0. 21） mm,respectively; the expression levels of interleukin-1β( IL^-1β) in all groups were（ 3. 67 ± 0. 17）,（ 16. 09 ± 0. 88）,（ 7. 26 ± 0. 65） and（ 6. 86 ± 0. 40） pg·m L^-1,respectively; the expression levels of matrix metalloproteinase 1（ MMP-1） in each group were（ 20. 41 ± 1. 20）,（ 67. 34 ± 4. 90）,（ 33. 18 ± 3. 63） and（ 29. 93 ± 2. 39） ng · m L^-1,respectively; TLR4 protein expression levels were 0. 25 ± 0. 03,1. 10 ± 0. 11,0. 45 ± 0. 05,0. 40 ± 0. 04,respectively; myeloid differentiation factor 88（ MyD88） protein expression levels were0. 36 ± 0. 04,0. 92 ± 0. 10,0. 43 ± 0. 05,0. 61 ± 0. 06,respectively. The above indicators were compared between the model group and the control group,the high-dose experimental group and the positive control group were compared with the model group,and the low-dose experimental group and the high-dose group,the differences were statistically significant（ all P < 0. 05）. Conclusion chikusetsusaponin Ⅳ a can inhibit inflammatory response and chondrocyte apoptosis to improve joint swelling in KOA rats,which is related to inhibition of TLR4/MyD88 signaling pathway.更多还原