目的 研究鹽酸小檗堿改善糖尿病腎病模型小鼠腎功能的作用及機制。方法 取8只C57BL/KS-db（db/m）雄性小鼠作為對照組，24只C57BL/KS-db（db/db）雄性小鼠隨機分為模型組、鹽酸二甲雙胍（300 mg·kg^-1）組和鹽酸小檗堿（300 mg·kg^-1）組，ig給藥，每天給藥1次，連續(xù)給藥8周，對照組和模型組ig相同體積的蒸餾水。稱體質量及腎臟質量，計算腎臟指數(shù)；采用全自動生化分析儀檢測尿液中尿肌酐、24 h尿蛋白，以及血樣中血肌酐、尿素氮的水平，計算肌酐清除率；采用蘇木素-伊紅（HE）染色、糖原過碘酸-雪夫（PAS）染色和馬松（Masson）染色檢測腎臟組織病理損傷程度；采用酶聯(lián)免疫吸附劑測定（ELISA）法檢測腎臟組織活性氧（ROS）、谷胱甘肽（GSH）、谷胱甘肽過氧化物酶（GSH-Px）、丙二醛（MDA）、超氧化物歧化酶（SOD）、過氧化氫酶（CAT）、白細胞介素-1β（IL-1β）、白細胞介素-6（IL-6）、腫瘤壞死因子-α （TNF-α）、單核細胞趨化蛋白-1 （MCP-1）水平；采用實時熒光定量PCR （qRT-PCR）法檢測腎臟組織LINC01619/miR-27a表達水平；采用Western blotting法檢測腎臟組織叉頭框蛋白O1 （FOXO1）/葡萄糖調節(jié)蛋白78（GRP78）/C/EBP同源蛋白（CHOP）蛋白表達情況。結果 與模型組比較，鹽酸小檗堿組空腹血糖、體質量、腎臟指數(shù)、24 h尿蛋白、血肌酐和血尿素氮顯著降低（P<0.01），尿肌酐和肌酐清除率顯著升高（P<0.01）；腎臟組織病理損傷程度明顯改善；腎臟組織ROS和MDA水平顯著降低（P<0.001），GSH、GSH-Px、CAT和SOD活性顯著升高（P<0.05）；腎臟組織中IL-1β、IL-6、TNF-α和MCP-1水平顯著下降（P<0.05）；腎臟組織中LINC01619表達顯著升高（P<0.01），miR-27a表達顯著降低（P<0.01）；腎臟組織中FOXO1蛋白表達顯著升高（P<0.01），而GRP78和CHOP蛋白表達顯著降低（P<0.01）。結論 鹽酸小檗堿可改善db/db小鼠的腎功能，其作用機制可能與調控LINC01619/miR-27a/FOXO1通路，改善內質網(wǎng)應激有關。

Objective To study the effect and mechanism of berberine hydrochloride on improving renal function in diabetic nephropathy mice.Methods Eight C57BL/KS-db (db/m) male mice were taken as control group. Twenty four C57BL/KS-db (db/db) male mice were randomly divided into model group, metformin (MET, 300 mg·kg^-1) group and berberine hydrochloride (300 mg·kg^-1) group. Drugs were ig given once a day for eight weeks. Body weight and kidney weight were weighed to calculate kidney index.Fasting blood glucose, urinary creatinine, 24 h urinary protein, blood creatinine and urea nitrogen were measured. HE staining, PAS staining and Masson staining were used to detect the degree of pathological injury of renal tissue. Reactive oxygen species (ROS), glutathione (GSH), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), interleukin-1 β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor -α (TNF-α), monocytes Chemotactic protein-1 (MCP-1) in renal tissue were detected by ELISA. The expression level of LINC01619/miR-27a in renal tissue were detected by real-time fluorescent quantitative PCR (qRT-PCR). The expression of FoxO1/GRP78/CHOP protein in renal tissue were detected by Western blotting. Results Compared with model group, fasting blood glucose, body mass, renal index, 24-hour urinary protein, blood creatinine and urea nitrogen in berberine hydrochloride group were significantly decreased (P<0.01), and urinary creatinine and creatinine clearance were significantly increased (P<0.01); The degree of pathological injury of renal tissue was significantly significantly improved; ROS and MDA in renal tissue were significantly decreased (P<0.001), GSH, GSH-Px, CAT and SOD were significantly increased (P<0.05). IL-1β, IL-6, TNF- α and MCP-1 were significantly decreased (P<0.05); The expression of LINC01619 was significantly increased (P<0.01), and the expression of miR-27a was significantly decreased (P<0.01). The expression of FOXO1 was significantly increased (P<0.01), while the expression of GRP78 and CHOP were significantly decreased (P<0.01). Conclusion Berberine hydrochloride can improve the renal function of db/db mice, and its mechanism may be related to regulating LINC01619/miR-27a/FOXO1 pathway and improving endoplasmic reticulum stress.

R285.5

國家自然科學基金資助項目（81803799）