目的 研究原儿茶醛对环磷酰胺（CTX）所致急性肾损伤的预防作用及其机制。方法 将 24 只 SPF 级雄性昆明种小鼠随机分为对照组、模型组及原儿茶醛低、高剂量（15、30 mg·kg^-1）组，每组各 6 只。对照组和模型组 ig 给予 0.9% 氯化钠溶液，原儿茶醛低、高剂量组每日 1 次 ig 对应药物。连续给药 14 d，末次给药 1 h 后，除对照组外，其余各组单次 ip 给药CTX （200 mg·kg^-1）。次日，在称体质量麻醉后取血和肾脏，分离血清，检测小鼠血清肌酐 （CRE）、超氧化物歧化酶（SOD）和过氧化氢酶（CAT）等生化指标；采用苏木素-伊红（HE）染色观察肾脏病理损伤情况；采用荧光染色检测小鼠肾脏 TUNEL 的表达情况；采用 Western blotting 检测 B 淋巴细胞瘤 2（Bcl-2）和 Bcl-2 相关 X 蛋白（BAX）等凋亡相关蛋白的表达情况。结果 与对照组比较，模型组小鼠的肾脏指数显著降低（P＜0.01）；血清 CRE 水平显著升高（P＜0.001）；血清 SOD、CAT、谷胱甘肽过氧化物酶（GSH-Px）水平显著降低（P＜0.05、0.01、0.001），丙二醛（MDA）水平显著升高（P＜0.01）；模型组小鼠肾脏细胞排列错乱、可见明显的炎症细胞浸润，伴随肾小管空泡变性和肾小管扩张；模型组小鼠肾脏 TUNEL 阳性表达显著增多（P＜0.001）；且肾脏天冬氨酸特异性半胱氨酸蛋白酶 3（Caspase-3）和 Bcl-2 的表达显著下降（P＜0.01、0.001），而 cleaved-Caspase3、BAX 蛋白的表达显著上升（P＜0.01、0.001）。与模型组比较，原儿茶醛低、高剂量组小鼠肾脏指数均显著增加（P＜0.05）；原儿茶醛高剂量组小鼠血清中的 CRE 水平明显降低（P＜0.001）；原儿茶醛低、高剂量组小鼠血清中 SOD、CAT、GSH-Px 水平显著上升（P＜0.05、0.01、0.001），MDA 水平显著下降（P＜0.05）；原儿茶醛低、高剂量组肾脏组织细胞排列比较规整，炎症细胞浸润及肾小管空泡变性和肾小管扩张等病理改变少见；原儿茶醛低、高剂量组肾脏 TUNEL 阳性表达有所下降 （P＜0.01、0.001），Caspase-3 和 Bcl-2 蛋白表达显著上升 （P＜0.05、0.01、0.001），cleaved-Caspase-3 和 BAX 蛋白表达显著下降（P＜0.01、0.001），呈剂量相关性。结论 原儿茶醛可预防 CTX所致急性肾损伤，其机制可能与抗细胞凋亡有关。

Objective To explore the preventive effect and mechanism of protocatechuic aldehyde (PAL) on acute kidney injury induced by cyclophosphamide (CTX). Methods Twenty-four SPF male KM mice were randomly divided into normal control group, model group, low, high dose PAL group (15, 30 mg·kg^-1), with six mice in each group. Except for the normal control group and model group, which were given normal saline by gavage, the mice of other groups were given corresponding drugs by gavage once daily. After 14 d, all the mice were given a single intraperitoneal injection of CTX (200 mg·kg^-1) except for those of normal control group which were injected with normal saline. On the next day, after weighing and anesthesia, blood and kidneys were obtained. The serum was separated to detect biochemical indicators such as creatinine (CRE), superoxide dismutase (SOD), and catalase (CAT). Hematoxylin eosin (HE) staining was conducted to observe the changes in renal pathological damage. Fluorescence staining was made to detect the expression of TUNEL in mice kidneys. Western blotting was adopted to detect the expression of apoptosis-related proteins such as B-cell lymphoma-2 (Bcl-2) and Bcl-2-related X protein (BAX). Results Compared with the control group, the kidney index of the mice in the model group was significantly decreased (P<0.01). The serum CRE was significantly increased (P<0.001). The levels of serum SOD, CAT, and GSH-Px were significantly reduced (P<0.05, 0.01, 0.001), while the level of MDA was significantly increased (P<0.01). The kidney cells of the mice in model group were arranged in a disordered manner, with obvious infiltration of inflammatory cells, accompanied by tubular vacuolar degeneration and tubular dilation. The positive expression of TUNEL in the mice kidneys of the model group were significantly increased (P<0.001). Moreover, the expressions of Caspase-3 and Bcl-2 in the kidneys were significantly decreased (P<0.01, 0.001), while the expressions of cleaved-Caspase-3 and BAX were significantly increased (P<0.01, 0.001). Compared with the model group, the kidney indexes of the mice in PAL-treated groups were significantly increased (P<0.05). The serum CRE level of the mice in H-PAL-treated group was significantly reduced (P<0.001). The levels of SOD, CAT, and GSH-Px in the serum of the mice in PAL-treated groups were significantly increased (P<0.05, 0.01, 0.001), while the levels of MDA were significantly decreased (P<0.05). The arrangement of kidney cells in PAL treatment groups was relatively regular, with rare pathological changes such as inflammatory cell infiltration, tubular vacuolar degeneration, and tubular dilation. The positive expression of TUNEL in the kidneys of the PAL treatment groups was decreased (P<0.01, 0.001), the expressions of Caspase-3 and Bcl-2 were obviously increased (P<0.05, 0.01, 0.001), and the expressions of cleaved-Caspase-3 and BAX were remarkably decreased (P<0.01, 0.001) in a dose-dependent manner. Conclusion PAL could prevent acute kidney injury caused by CTX, and its mechanism might be related to anti-cell apoptosis.

R285.5

国家自然科学基金资助项目（81801522）；河北省自然科学基金中医药联合基金重点项目（H2023209038）；河北省高等学校科学技术研究项目（ZD2022141）；华北理工大学大学生创新创业训练计划项目（X2023279）