3-MCPD对雌、雄大鼠肾毒性影响的比较  

Comparison of effects of 3-MCPD on nephrotoxicity in female and male rats

作　　者：黄江利 黄静怡 苏伟谦 刘香梅 李玙萌 李培宁 何婷 刘思颖 全锦雯 黄宇锋 刘忠华[1,2] HUANG Jiangli;HUANG Jingyi;SU Weiqian;LIU Xiangmei;LI Yumeng;LI Peining;HE Ting;LIU Siying;QUAN Jinwen;HUANG Yufeng;LIU Zhonghua(College of Veterinary Medicine,South China Agricultural University,Guangzhou 510642,China;Laboratory Animal Center,South China Agricultural University,Guangzhou 510642,China;Guangzhou Quality Supervision and Testing Institute,Guangzhou 511447,China)

机构地区：[1]华南农业大学兽医学院,广东广州510642 [2]华南农业大学实验动物中心,广东广州510642 [3]广州质量监督检测研究院,广东广州511447

出　　处：《中国兽医学报》2025年第2期322-329,340,共9页Chinese Journal of Veterinary Science

基　　金：广州市市场监督管理局科技资助项目(2023KJ01)。

摘　　要：为研究3-氯-1,2-丙二醇(3-monochloropropanel-1,2-diol, 3-MCPD)对雌、雄SD大鼠的肾毒性影响,试验通过灌胃不同剂量的3-MCPD建立肾毒性模型,将80只SD大鼠随机分为4组:对照组(0 mg/kg 3-MCPD)、低剂量组(15 mg/kg 3-MCPD)、中剂量组(30 mg/kg 3-MCPD)、高剂量组(60 mg/kg 3-MCPD),雌、雄各1/2。每周记录大鼠体质量和摄食量,连续灌胃28 d后收集尿液、血液并采集肾脏组织,检测血液红细胞数(WBC)、白细胞数(RBC)、血红蛋白(HGB)、红细胞压积值(HCT)、肌酐(CREA)、血清尿素氮(BUN)及血磷(P)、血钙(Ca)指标;ELISA试剂盒测定尿液肾损伤分子(KIM-1)水平;组织病理学观察肾脏病理变化;转录组测序分析雌、雄大鼠差异基因。结果表明,3-MCPD不会显著影响雄性大鼠的生长,但高剂量会显著降低雌性大鼠的体质量及摄食量;高剂量组3-MCPD会造成雌、雄大鼠RBC、HGB、HCT水平显著下降,造成雌、雄大鼠KIM-1、P显著上升,Ca显著下降,但仅造成雌性大鼠CREA、BUN显著上升;组织病理学显示高剂量组的雄性大鼠肾脏仅出现轻度肾小管扩张、上皮细胞水肿、透明管型,而雌性大鼠出现大量肾小囊、透明管型、肾间质炎性细胞伴纤维化等严重病变;转录组测序显示高剂量组雌性大鼠差异基因有1 712个,高剂量组雄性大鼠差异基因有1 153个。KEGG富集分析表示高剂量组下雌、雄大鼠都会产生氧化应激和细胞凋亡,但3-MCPD可能还会通过抑制自噬、诱导铁死亡途径参与对雌性产生肾脏损伤的过程。以上结果表明高剂量3-MCPD会对雌性大鼠产生更显著的肾毒性作用。This study aims to determine the nephrotoxic effects of 3-monochloropropanel-1,2-diol(3-MCPD)on female and male SD rats.A nephrotoxicity model was established by gavage of dif-ferent doses of 3-MCPD,and 80 SD rats were randomly divided into four groups:the control group(0 mg/kg 3-MCPD),low-dose group(15 mg/kg 3-MCPD),medium-dose group(30 mg/kg 3-MCPD),high-dose group(60 mg/kg 3-MCPD),with half female and half male.The body mass and food intake of the rats were recorded weekly,and the urine and blood and kidney tissues were col-lected after 28 consecutive days of gavage,and the blood erythrocyte count(WBC),white blood cell count(RBC),hemoglobin(HGB),erythrocyte-compaction-transfer-value(HCT),creatinine(CREA),serum urea nitrogen(BUN),and the indexes of blood phosphorus(P)and calcium(Ca)were detected;the level of kidney injury molecule(KIM-1)was measured by ELISA kit;the renal pathological changes was observed by histopathology method;and transcriptome sequencing was used to analyze differential genes in female and male rats.The results showed that 3-MCPD did not significantly affect the growth of male rats,but high doses significantly reduced the weight and food intake of female rats.The high-dose group of 3-MCPD caused a significant decrease in RBC,HGB,and HCT levels in both male and female rats,resulting in a significant increase in KIM-1 and P,and a significant decrease in Ca,but only a significant increase in CREA and BUN in female rats.Histopathology showed that in the high-dose group of male rats,only mild renal tubular dilation,epithelial cell edema,and clear tubular type were observed in the kidneys,while in female rats,a large number of renal sacs,clear tubular type,and interstitial inflammatory cells with fibrosis were observed in the kidneys.Transcriptome sequencing showed 1712 differentially expressed genes in the high-dose group of female rats and 1153 differentially expressed genes in the high-dose group of male rats.KEGG enrichment analysis showed that both male and female rats in the high-dose group

关 键 词：3-MCPD 大鼠 性别差异 肾毒性 转录组测序 

分 类 号：S856.9[农业科学—临床兽医学]