目的 探索小檗堿對高尿酸血癥小鼠炎癥因子水平和氧化應激損傷的影響機制。方法 選取雄性SPF級昆明小鼠48只,分為對照組、模型組、苯溴馬隆(20 mg/kg)組和小檗堿低、中、高劑量(50、100、200 mg/kg)組,每組8只。除對照組ig等量蒸餾水外,其余各組采用ig氧嗪酸鉀和次黃嘌呤藥物建立高尿酸血癥小鼠模型,造模后苯溴馬隆組ip給予20 mg/kg苯溴馬隆,小檗堿低、中、高劑量組分別ig 50、100、200 mg/kg小檗堿,各組均連續(xù)給藥1周。檢測小鼠血清指標尿酸、肌酐(Cr)水平;ELISA法測定C反應蛋白(CRP)水平、超氧化物歧化酶(SOD)的活性及丙二醛(MDA)的含量;蘇木素-伊紅染色觀察小鼠腎臟病理組織變化情況;Western blotting法檢測腎臟尿酸轉(zhuǎn)運蛋白URAT1在小鼠體內(nèi)的表達水平。結(jié)果 與對照組相比,模型組小鼠血清尿酸、Cr、CRP水平、MDA含量和URAT1蛋白表達均顯著升高,SOD含量明顯減少(P<0.01)。與模型組相比,苯溴馬隆組和小檗堿50、100、200 mg/kg組小鼠血清尿酸、Cr、CRP水平、MDA含量和URAT1蛋白表達顯著降低,SOD含量明顯增加(P<0.05、0.01)。小鼠腎臟HE染色結(jié)果提示,與模型組相比,小檗堿50、100、200 mg/kg組腎臟病理性改變的程度均有所緩解。而小檗堿100、200 mg/kg組與苯溴馬隆組比較無明顯差異。結(jié)論 小檗堿能降低高尿酸血癥小鼠體內(nèi)炎癥水平,提高抗氧化能力。同時減輕高尿酸血癥小鼠血清尿酸水平,其機制與抑制URAT1表達相關。

Objective To explore the mechanism and therapeutic effects of berberine on the levels of inflammatory factors and oxidative stress damage in mice with hyperuricemia. Methods Forty-eight male SPF grade Kunming mice were selected and divided into control group, model group, benbromarone (20 mg/kg) group, and berberine (50, 100, and 200 mg/kg) groups, with 8 mice in each group. Except for the control group, which was given the same amount of distilled water intragastrically, the other groups were ig administered with potassium oxazine and hypoxanthine to establish hyperuricemia mouse model. After modeling, benzbromarone group was ip 20 mg/kg benzbromarone, and berberine group was ig administered with 50, 100, 200 mg/kg berberine for 1 week, respectively. Serum uric acid and creatinine (Cr) levels were detected. The level of C-reactive protein (CRP), the activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) were determined by ELISA. HE staining was used to observe the pathological changes of mouse kidney. The expression level of renal uric acid transporter URAT1 in mice was detected by Western Blotting method. Results Compared with the control group, the levels of serum uric acid, Cr, CRP, MDA content, and URAT1 protein in model group were significantly increased, SOD content decreased obviously (P＜0.01). Compared with model group, the levels of serum uric acid, Cr, CRP, MDA content, and URAT1 protein in benbromarone group and berberine 50, 100, and 200 mg/kg groups were significantly decreased, SOD content increased obviously (P＜0.05, 0.01). The results of HE staining of mouse kidney indicated that compared with model group, berberine 50, 100, and 200 mg/kg groups had some relief in the degree of renal pathological changes. There was no significant difference between berberine 100 and 200 mg/kg groups and benzbromarone group. Conclusion Berberine can reduce inflammation and increase antioxidant capacity in hyperuricemia mice. At the same time, the serum uric acid level of hyperuricemia mice was reduced, and the mechanism was related to the inhibition of URAT1 expression.

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湖南省自然科學基金資助項目(2018JJ3569);湖南省教育廳科學研究資助項目(18B538,19C0199);湖南省衛(wèi)生計生委科研資助項目(C20180139);湖南省大學生創(chuàng)新創(chuàng)業(yè)訓練計劃項目(S202110823058);長沙醫(yī)學院"中青年骨干教師培養(yǎng)計劃"專項經(jīng)費資助(湘教通[2021]29號)