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| 右归丸通过PI3K/Akt/mTOR信号通路对膝骨关节炎模型鼠软骨组织保护作用的研究 |
| Effect of Yougui pill on the protection of cartilage tissue through PI3K/Akt/mTOR signal pathway in knee osteoarthritis rats |
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| DOI：10.3969/j.issn.1006.7108.2020.03.002 |
| 中文关键词: 右归丸 膝骨关节炎 PI3K/Akt/mTOR信号通路 自噬 |
| 英文关键词:Yougui pill knee osteoarthritis PI3K/Akt/mTOR signal pathway autophagy |
| 基金项目:甘肃省高等学校创新能力提升项目(2019A-080)；甘肃省中医药管理局科研项目(GZK-2017-2)；敦煌医学与转化省部共建教育部重点实验室开放基金项目(DHYX17-08)；甘肃省高校中（藏）药化学与质量研究省级重点实验室开放基金项目（zzy-2018-01）；甘肃省高校大学生就业创业能力提升工程项目(6-1) |
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| 中文摘要: |
| 目的 研究右归丸对膝骨关节炎（ knee osteoarthritis，KOA）模型大鼠磷脂酰肌醇3-激酶（phosphatidyl inositol 3-kinase，PI3K）、蛋白激酶B（protein kinase B，Akt）、哺乳动物雷帕霉素靶蛋白 （mammalian target of rapamycin，mTOR）信号通路的影响。方法 采用改良Hulth法制备大鼠KOA模型，模型制备成功6周后用右归丸进行干预，灌胃 2个月后取材。HE法观察各组大鼠软骨组织病理形态改变并进行Mankin评分，实时荧光定量 PCR法检测各组大鼠软骨组织白细胞介素-1β （interleukin-1β，IL-1β）、基质金属蛋白酶-3（matrix metalloproteinase -3，MMP-3）和基质金属蛋白酶-13 （matrix metalloproteinase -13，MMP-13）的表达变化， Western blot法检测各组大鼠软骨组织磷脂酰肌醇3-激酶（phosphatidyl inositol 3-kinase，PI3K）、磷酸化的蛋白激酶B（phosphorylated protein kinase B，pAkt）、磷酸化的哺乳动物雷帕霉素靶蛋白 （phosphorylated mammalian target of rapamycin，pmTOR）和Beclin1的蛋白表达。结果 与假手术组比较，模型组大鼠软骨组织Makin 评分明显升高，软骨组织IL-1β、MMP-3和MMP-13的基因表达均明显升高，软骨组织PI3K、pAkt和pmTOR的蛋白表达均明显升高（P<0.01）；而模型组大鼠软骨组织Beclin1的蛋白表达明显降低（P<0.01）；模型组关节软骨边缘严重破坏，软骨细胞排列紊乱。与模型组相比，右归丸组大鼠软骨组织Makin 评分明显降低，软骨组织IL-1β、MMP-3和MMP-13的基因表达均明显降低，软骨组织PI3K、pAkt和pmTOR的蛋白表达均明显降低，Beclin1的蛋白表达明显升高（P<0.05或P<0.01），其软骨结构趋于正常，软骨细胞分布偶见不均，关节软骨表面欠光滑。结论 右归丸可能是通过抑制IL-1β、MMP-3、MMP-13、PI3K、pAkt、pmTOR的表达和增强Beclin1的表达来达到治疗KOA的目的。 |
| 英文摘要: |
| Objective To explore the effect of Yougui pill on phosphatidyl inositol 3-kinase (PI3K)/ protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signal pathway in knee osteoarthritis (KOA) rat model. Methods The modified Hulth method was used to establish the rat KOA model. After 6 weeks, the rats were gavaged with corresponding drugs for 8 weeks. The morphological change of articular cartilage in each group was observed with HE staining and scored with Mankin method. The gene levels of IL-1β, MMP-3, and MMP-13 were detected with qRT-PCR. The protein expressions of PI3K, pAkt, mTOR, and Beclin1 were examined with Western blotting. Results Compared with those in the sham group, the Mankin score raised obviously, the gene expressions of IL-1β, MMP-3 and MMP-13 increased significantly, and the protein expressions of PI3K, pAkt, and mTOR increased significantly in the model group (P<0.01). The protein expression of Beclin1 reduced significantly in the model group (P<0.01). The articular cartilage was seriously damaged, and chondrocytes were arranged in disorder, in rats of model group. Compared with those in the model group, the Mankin score declined obviously, the gene expressions of IL-1β, MMP-3, and MMP-13 decreased significantly, and the protein expressions of PI3K, pAkt, and mTOR decreased significantly (P<0.05 or P<0.01) in rats of Yougui pill group. The protein expression of Beclin1 increased significantly in rats of Yougui pill group (P<0.01). The cartilage structure tended to be normal, the chondrocytes distribution was uneven, and the articular cartilage surface was not smooth in rats of Yougui pill group. Conclusion Yougui pill has the treatment effect on KOA through inhibition of IL-1β, MMP-3, MMP-1, PI3K, pAkt, and pmTOR expression and promotion of Beclin1 expression. |
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