益智仁调节SYK/CARD9/NF-κB信号通路抑制单侧输尿管梗阻大鼠肾纤维化的机制研究OA
Mechanism of Alpinia Oxyphyllae Fructus in Modulating SYK/CARD9/NF-κB Signaling Pathway to Inhibit Renal Fibrosis in Rats with Unilateral Ureteral Obstruction
目的:探讨益智仁(Alpinia Oxyphyllae Fructus,AOF)通过脾酪氨酸激酶(SYK)/半胱氨酸酶募集结构域蛋白9(CARD9)/核因子-κB(NF-κB)通路对单侧输尿管梗阻(UUO)大鼠肾纤维化的抑制作用及其机制.方法:将30只雄性Wistar大鼠随机分为假手术组(Sham组)、UUO组、AOF低剂量组(AOF-L组)、中剂量组(AOF-M组)、高剂量组(AOF-H组).采用单侧输尿管结扎法建立UUO模型.AOF各剂量组分别于手术当天开始给予对应剂量AOF浓煎剂灌胃,每日1次,连续21 d.术后第21天取材,利用生化检测各组大鼠的尿素氮(BUN)和肌酐(SCr);苏木素-伊红(HE)染色、Masson染色观察病理改变;免疫组化检测转化生长因子-β1(TGF-β1)、α-平滑肌肌动蛋白(α-SMA)、纤维连接蛋白(FN)表达;Western Blot法检测SYK/CARD9/NF-κB通路相关蛋白表达水平.结果:与Sham组相比,UUO组SCr、BUN升高(P＜0.05),病理可见广泛肾小管扩张,管腔形态不规则,上皮细胞变性、坏死,间质明显炎性细胞浸润,通路相关蛋白p-SYK/SYK、CARD9、p-NF-κB p65/NF-κB p65及肾纤维化相关蛋白TGF-β1、α-SMA、FN的相对表达水平均升高(P＜0.05);与UUO组相比,AOF治疗后大鼠的SCr、BUN水平降低(P＜0.05),肾组织病变和胶原沉积减轻,通路相关蛋白p-SYK/SYK、CARD9、p-NF-κB p65/NF-κB p65相对表达水平下调(P＜0.05),肾纤维化相关蛋白TGF-β1、α-SMA、FN的表达水平亦降低(P＜0.05),且各指标变化与剂量相关,以AOF-H组改善最为显著(P＜0.05).结论:AOF能改善UUO大鼠的肾纤维化,其作用机制可能与阻断SYK/CARD9/NF-κB通路有关.
Objective:To investigate the inhibitory effects of Alpinia Oxyphyllae Fructus(AOF)on renal fibrosis in rats with unilateral ureteral obstruction(UUO)via SYK/CARD9/NF-κB signaling pathway,and to elucidate the underlying mechanisms.Methods:Thirty male Wistar rats were randomly divided into the sham surgery group(Sham group),UUO group,low-dose AOF group(AOF-L group),medium-dose AOF group(AOF-M group),and high-dose AOF group(AOF-H group).A UUO model was established by unilateral ureteral ligation.Starting on the day of surgery,rats in each AOF dose group were administered the corresponding dose of AOF concentrated decoction via gavage once daily for 21 consecutive days.Tissue samples were collected on day 21 after the surgery.Biochemical assays were used to measure blood urea nitrogen(BUN)and serum creatinine(SCr)in rats from each group;hematoxylin-eosin(HE)and Masson's staining were used to observe histological changes;immunohistochemistry was used to detect the expression of transforming growth factor-β1(TGF-β1),α-smooth muscle actin(α-SMA),and fibronectin(FN);and Western blot analysis was used to assess the expression levels of proteins related to the SYK/CARD9/NF-κB signaling pathway.Results:Compared with the Sham group,the UUO group exhibited elevated SCr and BUN(P＜0.05).Histopathological examination revealed widespread tubular dilation,irregular tubular lumen morphology,epithelial cell degeneration and necrosis,and significant inflammatory cell infiltration in the interstitium.The relative expression levels of signaling pathway-related proteins p-SYK/SYK,CARD9,p-NF-κB p65/NF-κB p65,and renal fibrosis-associated proteins TGF-β1,α-SMA,and FN were all elevated(P＜0.05).Compared with the UUO group,rats treated with AOF showed reduced SCr and BUN levels(P＜0.05),alleviated renal tissue lesions and collagen deposition,downregulated p-SYK/SYK,CARD9,p-NF-κB p65/NF-κB p65,and reduced TGF-β1,α-SMA,and FN(P＜0.05).Furthermore,changes in these indicators were dose-dependent,with the most significant improvement observed in the AOF-H group(P＜0.05).Conclusion:AOF can improve renal fibrosis in UUO rats,and its mechanism of action may be related to the inhibition of the SYK/CARD9/NF-κB pathway.
任姝畅;邹艳红
佳木斯大学,黑龙江佳木斯 154000佳木斯大学第一附属医院,黑龙江佳木斯 154000
医药卫生
益智仁肾纤维化单侧输尿管梗阻脾酪氨酸激酶半胱氨酸酶募集结构域蛋白9核因子-κB
AOFrenal fibrosisunilateral ureteral obstructionspleen tyrosine kinasecystatin-recruiting domain protein 9nuclear factor-κB
《河北中医药学报》 2026 (2)
40-45,54,7
黑龙江省教育厅科研基础研究项目(2020-KYYWF-0286)
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