降浊四妙散通过降低血尿酸水平及抑制NLRP3 炎症小体 对大鼠高尿酸血症及其肾损伤的改善作用研究. (Chinese)

Objective: To explore the improvement effect of Jiangzhuo Simiao Powder on hyperuricemia and renal injury in rats by reducing serum uric acid level and inhibiting NLRP3 inflammasome. Methods: Twenty-eight SD rats were randomly divided into control group, potassium oxyacid(OA) model group, OA+SMS group, and OA+allopurinol group, among them, the dose of SMS is based on laboratory animal substance management standards(10 times the adult dose per kilogram of body weight); Allopurinol was dissolved in the drinking water of the OA + allopurinol group(concentration, 150 mg/L); The control group and the OA group were given the same amount of distilled water(the intragastric volume was controlled at 2 m L/d) for 7 weeks. To investigate the mediating effect of SMS on renal mitochondrial reactive oxygen species(ROS) and oxidative stress(OS) products, protein expression of NLRP3-ASC-caspase-1axis. Results:(1) The data of control group, OA model and treatment group were significantly different(P＜0.05). At the end of the 7th week, the total uric acid excretion in the model group was significantly higher than that in the control group(P＜0.05), and the SZF group and allopurinol group were significantly higher than those in the OA group(P＜0.05).(2) Compared with the control group, the levels of BUN and Scr in the OA group were significantly increased(P＜0.05), while the levels of BUN and Scr in the rats treated with SMS and allopurinol decreased(P＜0.05).(3) In renal tissue structure, for the OA+SZF and OA+allopurinol groups, the epithelial cell swelling, vacuolar degeneration and inflammatory cell infiltration in the proximal renal tubules were reduced.(4) The oxidative stress indexes in renal tissue of OA-induced hyperuricemia rats were all increased(P＜0.05); namely, superoxide dismutase(SOD), catalase(CAT) and glutathione There was a significant imbalance between peroxidases, while SMS and allopurinol intervention could significantly restore the dynamic balance of the above oxidative stress response indicators(P＜0.05).(5) The expression of TXNIP m RNA and protein in kidney tissue of rats in OA group was significantly higher than that in other groups(P＜0.05), while SMS and allopurinol effectively inhibited the expression of TXNIP m RNA and protein(P＜0.05); m RNA and protein expression in the murine NLRP3-ASC-caspase-1 axis was elevated(P＜0.05). The activation of NLRP3-ASC-caspase-1 axis in the SMS group was significantly inhibited(P＜0.05). Conclusion: SMS attenuated tubular damage and inflammatory infiltration by reducing blood uric acid levels in reducing renal damage, while inhibiting the NLRP3 inflammasome activation triggered by mitochondrial ROS. [ABSTRACT FROM AUTHOR]

目的：探究降浊四妙散通过降低血尿酸水平及抑制NLRP3 炎症小体对大鼠高尿酸血症及其肾损伤的改善作用。方法：将28 只SD 大鼠随机分为对照组、氧酸钾(OA)模型组、OA+SMS 组、OA+ 别嘌醇组，其中，SMS 的剂量基于实验动物物质管理标准(每 公斤体重成人剂量的10 倍)；别嘌醇溶解在OA+ 别嘌醇组的饮用水中(浓度，150 mg/L)；对照组和OA 组给予等量的蒸馏水(胃 内容量控制在2 mL/d)，持续7 周。探讨SMS 对肾线粒体活性氧(ROS)和氧化应激(OS)产物、NLRP3-ASC-caspase-1 轴的蛋白表 达。结果：(1)对照组、OA 模型和治疗组的数据存在显著差异(P<0.05)。在第7 周结束时，模型组总尿酸排泄量显著高于对照组 (P<0.05)，SZF 组和别嘌醇组显著高于OA 组(P<0.05)。(2)与对照组相比，OA 组的BUN 和Scr 水平显著升高(P<0.05)，而接受 SMS 和别嘌醇治疗大鼠的BUN 和Scr 水平下降(P<0.05)。(3)肾组织结构中，对于OA+SZF 和OA+ 别嘌呤醇组，肾近端肾小管 上皮细胞肿胀、空泡变性和炎性细胞浸润减少。(4)OA 诱导的高尿酸血症大鼠肾组织中氧化应激指标均升高(P＜0.05)；即超氧 化物歧化酶(SOD)、过氧化氢酶(CAT)和谷胱甘肽过氧化物酶之间存在显著的不平衡，而SMS 和别嘌醇干预可显著回复以上氧 化应激反应指标的动态平衡(P＜0.05)。(5)OA 组大鼠肾组织中TXNIP mRNA 和蛋白表达显著高于其他组(P<0.05)，而SMS 和 别嘌醇有效抑制TXNIP mRNA 和蛋白表达(P<0.05)；高尿酸血症大鼠NLRP3-ASC-caspase-1 轴中的mRNA 和蛋白质表达升高 (P<0.05)。SMS 干预后组NLRP3-ASC-caspase-1 轴的激活显著被抑制(P<0.05)。结论：SMS 通过降低高尿酸血症实验大鼠肾脏中 血尿酸水平，进而减轻肾损害，同时其可抑制线粒体ROS 触发的NLRP3 炎性体激活来减轻肾小管损伤和炎症浸润。 [ABSTRACT FROM AUTHOR]

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