茶多酚对D-半乳糖诱导致大鼠肾脏损害的保护作用及其机制

目的探讨茶多酚(teapolyphenols,TP)对D-半乳糖诱导致大鼠肾脏损害的保护作用及其作用机制。方法D-半乳糖(150mg/kgbw)连续腹腔注射(ip)8w,诱导大鼠糖基化肾脏损伤,并于第3w开始灌胃给予茶多酚高、中、低(150,75,37.5mg/kgbw)剂量处理6w,阳性对照药物给与维生素E(250mg/kgbw)和氨基胍(150mg/kgbw)。测定大鼠血糖,糖化血红蛋白,血清果糖胺;测定血红细胞醛糖还原酶活性和晚期糖基化终末产物(AGEs)含量;测定肾脏组织中AGEs、MDA含量,SOD和GSH-Px活性;测定尿蛋白含量,血尿素氮和血肌酐含量;流式细胞仪检测肾脏细胞凋亡情况。结果D-半乳糖处理8w后,模型大鼠2h血糖和血红细胞醛糖还原酶活性明显升高,糖化产物形成增多;肾组织中AGEs和MDA含量明显升高,SOD及GSH-Px活性下降,尿蛋白、血尿素氮和血肌酐量明显增加,肾细胞凋亡率明显增加。茶多酚处理6w后,高、中剂量可以明显抑制D-半乳糖引起的全身和肾脏糖基化反应,降低肾组织中AGEs和MDA含量,并提高肾脏组织抗氧化能力,降低尿蛋白、血尿素氮和血肌酐含量及肾细胞的凋亡率。结论茶多酚通过抑制糖基化反应和提高肾脏组织抗氧化能力,对D-半乳糖诱导的肾脏损伤具有保护作用。

THE PROTECTIVE EFFECT OF TEA POLYPHENOLS ON RENAL DAMAGE IN RATS INDUCED BY D-GALACTOSE AND ITS MECHANISM

Objective To investigate the effect of tea polyphenols (TP) on renal damage in rats model induced by D-galactose. Methods Rats were injected with D-galactose (150 mg/kgd), ip for 8 w, to induce renal damage. From the 3rd week, TP (150, 75, 37.5 mg/kg·d), aminoguanidine (150 mg/kg) and vitamin E (150 mg/kg) were administered with D-galactose for 6 w. After treatment, fasting blood glucose and 2 h blood glucose in oral glucose tolerance test were measured. The levels of HbAlC and fructosamine in serum, the activity of aldose reductase and content of advanced glycation end products (AGEs) in plasma and in kidney tissues and the activity of SOD, GSH-Px, and the contents of MDA in kidney tissues were measured, and 24h urinary protein, blood urea nitrogen (BUN) and serum creatinine (Cr) were detected. The apoptosis of renal cells were detected by flow cytometer. Results After treatment of D-galactose for 8 w, 2h glucose level in oral glucose talerance test was increased significantly, the activity of aldose reductase and the content of AGES were increased significantly in blood. The levels of AGEs and MDA in renal tissues were also enhanced significantly. However, the activities of SOD and GSH-Px decreased. Additionally, the contents of 24h urine protein, BUN, Cr and the apoptotic rate of renal cells were increased significantly. High and middle dose of TP could can decrease the activity of aldose reductase in red blood cells, and inhibit the formation of glycation products in model rats induced by D-galactose. Also, TP could enhance the antioxidative activities and decrease the contents of AGEs and MDA in renal tissues. Mesnwhile, 24h urine protein, BUN and Cr and the apoptotic rate of renal cells were increased significantly. Conclusion TP can inhibit glycation reaction induced by D-galactose and then protect renal from damage caused by glycation.