目的 研究原兒茶醛對環(huán)磷酰胺（CTX）所致急性腎損傷的預(yù)防作用及其機制。方法 將 24 只 SPF 級雄性昆明種小鼠隨機分為對照組、模型組及原兒茶醛低、高劑量（15、30 mg·kg^-1）組，每組各 6 只。對照組和模型組 ig 給予 0.9% 氯化鈉溶液，原兒茶醛低、高劑量組每日 1 次 ig 對應(yīng)藥物。連續(xù)給藥 14 d，末次給藥 1 h 后，除對照組外，其余各組單次 ip 給藥CTX （200 mg·kg^-1）。次日，在稱體質(zhì)量麻醉后取血和腎臟，分離血清，檢測小鼠血清肌酐 （CRE）、超氧化物歧化酶（SOD）和過氧化氫酶（CAT）等生化指標(biāo)；采用蘇木素-伊紅（HE）染色觀察腎臟病理損傷情況；采用熒光染色檢測小鼠腎臟 TUNEL 的表達情況；采用 Western blotting 檢測 B 淋巴細胞瘤 2（Bcl-2）和 Bcl-2 相關(guān) X 蛋白（BAX）等凋亡相關(guān)蛋白的表達情況。結(jié)果 與對照組比較，模型組小鼠的腎臟指數(shù)顯著降低（P＜0.01）；血清 CRE 水平顯著升高（P＜0.001）；血清 SOD、CAT、谷胱甘肽過氧化物酶（GSH-Px）水平顯著降低（P＜0.05、0.01、0.001），丙二醛（MDA）水平顯著升高（P＜0.01）；模型組小鼠腎臟細胞排列錯亂、可見明顯的炎癥細胞浸潤，伴隨腎小管空泡變性和腎小管擴張；模型組小鼠腎臟 TUNEL 陽性表達顯著增多（P＜0.001）；且腎臟天冬氨酸特異性半胱氨酸蛋白酶 3（Caspase-3）和 Bcl-2 的表達顯著下降（P＜0.01、0.001），而 cleaved-Caspase3、BAX 蛋白的表達顯著上升（P＜0.01、0.001）。與模型組比較，原兒茶醛低、高劑量組小鼠腎臟指數(shù)均顯著增加（P＜0.05）；原兒茶醛高劑量組小鼠血清中的 CRE 水平明顯降低（P＜0.001）；原兒茶醛低、高劑量組小鼠血清中 SOD、CAT、GSH-Px 水平顯著上升（P＜0.05、0.01、0.001），MDA 水平顯著下降（P＜0.05）；原兒茶醛低、高劑量組腎臟組織細胞排列比較規(guī)整，炎癥細胞浸潤及腎小管空泡變性和腎小管擴張等病理改變少見；原兒茶醛低、高劑量組腎臟 TUNEL 陽性表達有所下降 （P＜0.01、0.001），Caspase-3 和 Bcl-2 蛋白表達顯著上升 （P＜0.05、0.01、0.001），cleaved-Caspase-3 和 BAX 蛋白表達顯著下降（P＜0.01、0.001），呈劑量相關(guān)性。結(jié)論 原兒茶醛可預(yù)防 CTX所致急性腎損傷，其機制可能與抗細胞凋亡有關(guān)。

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

國家自然科學(xué)基金資助項目（81801522）；河北省自然科學(xué)基金中醫(yī)藥聯(lián)合基金重點項目（H2023209038）；河北省高等學(xué)?？茖W(xué)技術(shù)研究項目（ZD2022141）；華北理工大學(xué)大學(xué)生創(chuàng)新創(chuàng)業(yè)訓(xùn)練計劃項目（X2023279）