X线造影剂对高胆固醇血症大鼠的肾毒性及己酮可可碱的保护作用

目的 比较不同渗透浓度X线造影剂对高胆固醇血症大鼠的肾毒性，探讨己酮可可碱（PTX）对造影剂肾毒性是否有保护作用。 方法 48只健康雄性SD大鼠，随机分为正常饮食组8只（NN组）和高胆固醇饮食组40只（H组，4%胆固醇+1%胆酸钠）。8周末，高胆固醇饮食组随机分为5组，每组8只，分别为高胆固醇饮食组（HN组）、高胆固醇+低渗造影剂组（HL组）、高胆固醇+等渗造影剂组（HI组）、高胆固醇饮食+高渗造影剂组（HH组）、高胆固醇+高渗造影剂+PTX组（HHP组）。在注射造影剂后48 h测定各组大鼠的血清总胆固醇、三酰甘油、血清肌酐、内生肌酐清除率（Ccr）、钠钾排泄分数及血管紧张素Ⅱ（AngⅡ）的浓度；光镜下观察肾组织学改变；免疫组化法检测肾组织NF-κB的蛋白表达；原位细胞调亡（TUNEL）染色检测肾小管上皮细胞的凋亡。 结果 所有给予高胆固醇饮食的大鼠血清总胆固醇水平明显增高（P < 0.05）。HH组的血清肌酐、钠钾排泄分数及血浆Ang Ⅱ水平均分别明显高于HHP组、HL组及HI组（P < 0.05）；HH组Ccr水平（0.11±0.02） ml·min-1·（100 g）-1]则明显低于HHP组（0.43±0.03） ml·min-1·（100 g）-1]、HL组（0.25±0.02） ml·min-1·（100 g）-1]和HI组（0.27±0.03） ml·min-1·（100 g）-1]（P < 0.05）。组织病理显示，HH组大鼠肾小管上皮细胞发生明显的变性和坏死，肾小管上皮细胞凋亡率（89.60%±6.40%）明显高于其他各组NN组（2.40％±0.77％）、HN组（5.60％±1.08％）、HHP组（8.91％±1.44％）、HL组（63.34％±11.97％）、HI组（61.50％±9.40％）]（P < 0.05）。肾组织NF-κB阳性细胞的平均灰度值明显低于其他各组（P < 0.05）；而HL组和HI组间上述指标比较差异无统计学意义 （P > 0.05）。 结论 高胆固醇血症环境下注射不同渗透浓度X线造影剂均可致造影剂肾损害。PTX对高胆固醇血症环境下所致的造影剂肾毒性有保护作用。

Nephrotoxicity of X-ray contrast media and protective effect of pentoxifylline in rats with hypercholesterolemia

Objective To evaluate the nephrotoxicity induced by radiographic contrast media with different osmolality in rats with hypercholesterolemia, and to explore the protective effect of pentoxifylline. Methods Forty-eight healthy SD male rats were randomly divided into normal dietary group (NN, n =8) and high cholesterol supplemented dietary group (H, 4% cholesterol and 1% cholic acid, n=40). At the end of 8th week, the rats with high cholesterol diet were randomly divided into five subgroups (n=8, respectively): high cholesterol diet group(HN), high cholesterol plus iso-osmolar contrast media (iodixanol, IOCM) group (HI), high cholesterol plus low-osmolar contrast media (iohexle, LOCM) group (HL), high cholesterol diet plus high-osmolar contrast media (diatrizoate, HOCM) group (HH) and high cholesterol plus HOCM plus pentoxifylline group (HHP). Forty-eight hours after contrast media injection, the rats were executed and blood samples were prepared to determine total cholesterol, triglyceride, serum creatinine, creatinine clearance(Ccr), fractional excretion of sodium and potassium(FeNa, FeK), and angtension Ⅱ (Ang Ⅱ) levels. The renal injury was assessed by HE staining and TUNEL staining, respectively. The expression of NF-κB protein in the renal tissue was detected by using immunohistocbemical method. Results An increase of cholesterol was observed in all the rats with high cholesterol diet. Scr, FeNa%, FeK% and Ang Ⅱ levels of rats in HH group were obviously higher than those in HL and HI groups respectively. Ccr in HH group (0.11±0.02) ml·min-1·(100 g)-1] was significantly lower than that in HHP group (0.43±0.03) ml·min-1·(100 g)-1], HL group (0.25±0.02) ml·min-1·(100 g)-1] or HI group (0.27±0.03) ml·min-1,(100 g)-1] (P<0.05). TUNEL staining showed that the pewentage of apoptotic cells in HH group (89.60±6.40)% ] was higher than that of the other groups NN (2.40±0.77)%, HN (5.60±1.08)%, HHP (8.91±1.44)%, HL (63.34±11.97)% and HI (61.50±9.40)%]. Immunohistochemistry staining showed that the average gray value of NF-κB positive cells in HH group decreased (P<0.05). There were no significant differences of all indices between HL and HI groups (P0.05). Conclusions Contrast media can cause kidney injuries in the rats with hypercholesterolemia. PTX can protect the renal tissue from nephrotoxicity induced by HOCM in hypercholesterolemia.