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[胶囊通过抑制PTEN/PI3K/AKT信号通路减轻痛风性关节炎大鼠的炎症及尿酸和脂质代谢失衡]

[ Capsule alleviates inflammation and uric acid and lipid metabolism imbalance in rats with gouty arthritis by inhibiting the PTEN/PI3K/AKT signaling pathway].

作者信息

Zhang X, Liu J, Han Q, Chen Y, Ding X, Chen X

机构信息

The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei 230011, China.

Anhui University of Chinese Medicine, Hefei 230012, China.

出版信息

Nan Fang Yi Ke Da Xue Xue Bao. 2024 Aug 20;44(8):1450-1458. doi: 10.12122/j.issn.1673-4254.2024.08.03.

Abstract

OBJECTIVE

To investigate the effects of Capsule (HQC) on inflammation and uric acid and lipid metabolism in rats with gouty arthritis (GA) and its mechanism.

METHODS

SD rat models of GA established by injecting monosodium urate into the right ankle joint were treated with saline, colchicine and HQC at low, medium and high doses (=10) by gavage for 7 days. Toe swelling of the rats was detected at 4, 8, 24, 48 and 72 h after modeling, and synovial histological changes were observed with HE staining. Serum levels of interleukin-10 (IL-10), IL-18, tumor necrosis factor- (TNF-), transforming growth factor-β1 (TGF-β1), adiponectin, leptin, resistin and visfatin were measured by ELISA, and the levels of high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), total cholesterol (TC), and uric acid (BUA) were detected. RTqPCR and Western blotting were used to detect the mRNA expressions of phosphatase and tensin homolog (PTEN), phosphatidylinositol-3-kinase (PI3K) and protein kinase B (AKT) and the protein expressions of PTEN, PI3K, p-PI3K, AKT and p-AKT.

RESULTS

The rat models of GA showed obvious toe swelling, which reached the peak level at 48 h. HE staining revealed massive inflammatory cell infiltration and synovial tissue hyperplasia. The rat models showed significantly increased expressions of TNF-, TGF-β1, IL-18, TC, TG, leptin, resistin and visfatin, BUA, p-PI3K, and p-AKT and lowered levels of IL-10, APN, HDL-C, and PTEN. Treatment with HQC and colchicine obviously improved these changes and alleviated synovial pathologies and toe swelling in the rat models.

CONCLUSION

HQC can improve inflammation and correct the imbalance of uric acid and lipid metabolism in GA rats possibly by inhibiting the PTEN/PI3K/AKT signaling pathway.

摘要

目的

探讨黄葵胶囊(HQC)对痛风性关节炎(GA)大鼠炎症及尿酸、脂质代谢的影响及其作用机制。

方法

将尿酸钠注入右踝关节建立GA的SD大鼠模型,分别用生理盐水、秋水仙碱及低、中、高剂量(n = 10)的HQC灌胃治疗7天。建模后4、8、24、48和72小时检测大鼠足趾肿胀情况,并用苏木精-伊红(HE)染色观察滑膜组织学变化。采用酶联免疫吸附测定法(ELISA)检测血清白细胞介素-10(IL-10)、IL-18、肿瘤坏死因子-α(TNF-α)、转化生长因子-β1(TGF-β1)、脂联素、瘦素、抵抗素和内脂素水平,检测高密度脂蛋白胆固醇(HDL-C)、甘油三酯(TG)、总胆固醇(TC)和尿酸(BUA)水平。采用逆转录定量聚合酶链反应(RTqPCR)和蛋白质免疫印迹法检测磷酸酶和张力蛋白同源物(PTEN)、磷脂酰肌醇-3-激酶(PI3K)和蛋白激酶B(AKT)的mRNA表达以及PTEN、PI3K、p-PI3K、AKT和p-AKT的蛋白表达。

结果

GA大鼠模型出现明显的足趾肿胀,在48小时达到峰值水平。HE染色显示大量炎性细胞浸润和滑膜组织增生。大鼠模型显示TNF-α、TGF-β1、IL-18、TC、TG、瘦素、抵抗素和内脂素、BUA、p-PI3K和p-AKT的表达显著增加,而IL-10、脂联素、HDL-C和PTEN水平降低。HQC和秋水仙碱治疗明显改善了这些变化,减轻了大鼠模型的滑膜病变和足趾肿胀。

结论

HQC可能通过抑制PTEN/PI3K/AKT信号通路改善GA大鼠的炎症,纠正尿酸和脂质代谢失衡。

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PTEN: an emerging target in rheumatoid arthritis?
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Qingre Huazhuo Jiangsuan Decoction promotes autophagy by inhibiting PI3K/AKT/mTOR signaling pathway to relieve acute gouty arthritis.
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