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柳玉佳, 杨烨晗, 吴伊莹, 贺选玲, 王莘智, 徐豫湘.通痹颗粒调控PI3K/Akt/mTOR信号通路治疗胶原诱导性关节炎大鼠的机制研究[J].湖南中医药大学学报,2026,46(7):1336-1344[点击复制] |
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| 通痹颗粒调控PI3K/Akt/mTOR信号通路治疗胶原诱导性关节炎大鼠的机制研究 |
| 柳玉佳,杨烨晗,吴伊莹,贺选玲,王莘智,徐豫湘 |
| (湖南中医药大学第一附属医院, 湖南 长沙 410007;湖南中医药大学第二附属医院, 湖南 长沙 410005) |
| 摘要: |
| 目的 观察通痹颗粒调控磷脂酰肌醇3激酶（PI3K）/蛋白激酶B（Akt）/雷帕霉素靶蛋白（mTOR）信号通路对胶原诱导性关节炎（CIA）大鼠的治疗作用及机制。方法 60只SD大鼠采用随机数字表法分为空白组、模型组、雷公藤多苷片组及低、中、高剂量通痹颗粒组，每组10只。空白组常规饲养，其余各组以牛Ⅱ型胶原建立CIA大鼠模型。造模成功后，空白组、模型组予以0.9%氯化钠注射液灌胃，雷公藤多苷片组给予雷公藤多苷片（0.024 g/kg）灌胃，低、中、高剂量通痹颗粒组分别给予（1.8、3.6、7.2 g/kg）通痹颗粒灌胃，每天1次，连续28 d。比较各组大鼠关节炎指数评分、关节肿胀度变化；HE染色观察大鼠滑膜组织病理学形态；RT-qPCR法及Western blot测定PI3K、Akt、mTOR及自噬标志蛋白Beclin-1、微管相关蛋白1轻链3Ⅱ（LC3-Ⅱ）mRNA及蛋白表达水平；ELISA测定白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）、基质金属蛋白酶（MMP）-1和MMP-13水平。结果 与空白组比较，模型组治疗第0、7、14、21、28天关节炎指数评分、关节肿胀度和PI3K、Akt、mTOR mRNA及蛋白表达水平均升高（P＜0.05），血清IL-1β、TNF-α、MMP-1、MMP-13水平均升高（P＜0.05）；Beclin-1、LC3-Ⅱ的mRNA及蛋白表达水平均降低（P＜0.05）。与模型组比较，雷公藤多苷片组和低、中、高剂量通痹颗粒组治疗第7、14、21、28天关节炎指数评分、关节肿胀度和PI3K、Akt、mTOR mRNA及蛋白表达水平均降低（P＜0.05），血清IL-1β、TNF-α、MMP-1、MMP-13水平均降低（P＜0.05）；Beclin-1、LC3-Ⅱ的mRNA及蛋白表达水平均升高（P＜0.05）。与雷公藤多苷片组比较，低、中剂量通痹颗粒组治疗后关节炎指数评分、关节肿胀度和PI3K、Akt、mTOR mRNA及蛋白表达水平均升高（P＜0.05），血清IL-1β、TNF-α、MMP-1水平均升高（P＜0.05），Beclin-1、LC3-Ⅱ的mRNA及蛋白表达水平均降低（P＜0.05）；高剂量通痹颗粒组关节炎指数评分、关节肿胀度和PI3K、Akt、mTOR mRNA及蛋白表达水平均降低（P＜0.05），血清IL-1β、TNF-α、MMP-1水平均均降低（P＜0.05），滑膜Beclin-1、LC3-Ⅱ的mRNA及蛋白表达水平均升高（P＜0.05）。模型组大鼠关节结构广泛破坏、形态紊乱，滑膜明显增厚，伴随大量炎症细胞浸润及新生血管增生；各给药组大鼠关节滑膜损伤均改善，关节侵蚀破坏减轻，滑膜增厚及炎症浸润明显减少，以高剂量通痹颗粒组改善情况最为显著。结论 通痹颗粒可有效改善CIA大鼠关节滑膜炎症，其作用机制可能与抑制PI3K/Akt/mTOR信号通路激活、提升滑膜细胞自噬水平相关，适用于痰瘀深伏的顽痹证候。 |
| 关键词: 类风湿关节炎|通痹颗粒|胶原诱导性关节炎|细胞自噬|PI3K/Akt/mTOR信号通路 |
| DOI：10.3969/j.issn.1674-070X.2026.07.004 |
| 投稿时间：2026-05-17 |
| 基金项目:湖南省医学学科A类建设项目（中医内科）（湘卫医发〔2025〕7号）；湖南省自然科学基金项目（2025JJ80928，2026JJ82264）；长沙市自然科学基金项目（kq2502047）。 |
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| Mechanism of Tongbi Granule in treating collagen-induced arthritic rats by regulating PI3K/Akt/mTOR signaling pathway |
| LIU Yujia, YANG Yehan, WU Yiying, HE Xuanling, WANG Shenzhi, XU Yuxiang |
| (The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410007, China;The Second Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410005, China) |
| Abstract: |
| Objective To observe the therapeutic effects and mechanism of Tongbi Granule in regulating the phosphati-dylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway in rats with collagen-induced arthritis (CIA). Methods Sixty SD rats were randomly divided into blank group, model group, Tripterygium Glycosides Tablet group, and low-, medium-, and high-dose Tongbi Granule groups, with 10 rats in each group. The blank group received routine feeding, while the other groups were used to establish CIA rat models using bovine type Ⅱ collagen. After successful modeling, the blank group and model group were given 0.9% sodium chloride injection by gavage; the Tripterygium Glycosides Tablet group received Tripterygium Glycosides Tablets (0.024 g/kg); and the low-, medium-, and high-dose Tongbi Granule groups received Tongbi Granule at doses of 1.8, 3.6, and 7.2 g/kg, respectively, once daily for 28 consecutive days. The arthritis index score and joint swelling degree were compared among groups. HE staining was used to observe the histopathological morphology of synovial tissue. RT-qPCR and Western blot were employed to determine the mRNA and protein expression levels of PI3K, Akt, mTOR, and the autophagy marker proteins Beclin-1 and microtubule-associated protein 1 light chain 3 Ⅱ (LC3-II). ELISA was used to measure the levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), matrix metalloproteinase-1 (MMP-1), and MMP-13. Results Compared with the blank group, the model group showed increased arthritis index scores and joint swelling on days 0, 7, 14, 21, and 28; elevated mRNA and protein expression levels of PI3K, Akt, and mTOR; and higher serum levels of IL-1β, TNF-α, MMP-1, and MMP-13 (P<0.05), while the mRNA and protein expression levels of Beclin-1 and LC3-Ⅱ decreased (P<0.05). Compared with the model group, the Tripterygium Glycosides Tablet group and all three Tongbi Granule dose groups exhibited decreased arthritis index scores and joint swelling on days 7, 14, 21, and 28; reduced mRNA and protein expression levels of PI3K, Akt, and mTOR; lower serum IL-1β, TNF-α, MMP-1, and MMP-13 levels (P<0.05); and increased mRNA and protein expression levels of Beclin-1 and LC3-Ⅱ (P<0.05). Compared with the Tripterygium Glycosides Tablet group, the low- and medium-dose Tongbi Granule groups showed higher arthritis index scores and joint swelling, elevated PI3K/Akt/mTOR mRNA and protein expression levels, and increased serum IL-1β, TNF-α, and MMP-1 levels (P<0.05), along with decreased Beclin-1 and LC3-Ⅱ mRNA and protein expression levels (P<0.05); the high-dose Tongbi Granule group showed decreased arthritis index scores and joint swelling, reduced PI3K/Akt/mTOR mRNA and protein expression levels, and lower serum IL-1β, TNF-α, and MMP-1 levels (P<0.05), while synovial Beclin-1 and LC3-Ⅱ mRNA and protein expression levles increased (P<0.05). In the model group, the joint structure was extensively damaged and disorganized, with marked synovial hyperplasia, abundant inflammatory cell infiltration, and neovascularization. In all treatment groups, synovial injury was ameliorated, with reduced joint erosion, synovial thickening, and inflammatory infiltration; the most pronounced improvement was observed in the high-dose Tongbi Granule group. Conclusion Tongbi Granule can effectively improve synovial inflammation in CIA rats, and its mechanism of action may be related to inhibition of the PI3K/Akt/mTOR signaling pathway and enhancement of synovial cell autophagy, making it suitable for treating intractable impediment pattern with deep-rooted phlegm and blood stasis. |
| Key words: rheumatoid arthritis|Tongbi Granule|collagen-induced arthritis|autophagy|PI3K/Akt/mTOR signaling pathway |
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