驱铅颗粒对铅中毒大鼠肾小管上皮细胞凋亡的干预作用

探讨益气化滞方驱铅颗粒对铅导致的肾小管上皮细胞凋亡的保护作用。方法：60只大鼠随机分为2组，其中空白组12只，饮用双蒸水；造模组48只，在饮水中添加0．02％醋酸铅，连续60d制作大鼠慢性铅中毒模型，然后将造模动物随机分为4组：模型组（不予任何治疗），驱铅颗粒高剂量组（按3．0g·k^-1·d“的剂量灌胃）、驱铅颗粒低剂量组（按0．6g·kg^-1·d^-1的剂量灌胃）、阳性对照组（依地酸钠钙加普鲁卡因肌内注射，50mg·kg^-1·d^-1），连续4d为1个疗程，休息4d后进行下1个疗程，连续干预7个疗程，连续60d后检测各组血Pb、肾Pb含量，并用TUNEL法检测各组动物肾组织的细胞凋亡；免疫组化方法检测肾组织Bcl．2蛋白表达，Western Blotting方法检测肾组织p53表达。结果：与空白组比较，模型组动物体质量、血色素及Bcl-2蛋白表达均有显著降低（P〈0．01），而血Pb、肾Pb、肾组织凋亡及p53蛋白表达均显著增高（P〈0．05）。与模型组比较。驱铅颗粒高剂量组体质量、血色素及肾小管Bcl-2表达均有显著增高（P〈0．05），血Pb、肾组织Pb、肾组织凋亡及p53蛋白表达均显著降低（P〈0．05）。结论：益气化滞方驱铅颗粒能降低动物血Pb和肾组织Pb含量，并通过抑制铅导致的p53高表达、促进Bcl-2表达而减轻肾小管上皮细胞凋亡，降低铅对肾组织的损伤。

Intervention on Apoptosis of Renal Tubular Epithelial Cell in Chronic Lead Poisoning Rats by Quqian Granules

To investigate the protective effect of Yiqi Huazhi recipe Quqian granules on rat renal tubular cell apoptosis induced by lead poisoning. Methods： Totally 60 Wistar rats were divided into 2 groups, 12 in the control group and the others in the model group. Chronic lead poisoning model was made by drinking 0.02% lead acetate water for 60 days. Then the lead poisoning rats were randomly divided into four groups, high-dose Quqian granules group （3.0 g ·kg^-1·d^-1 ）, low-dose Quqian granules group （0.6 g · kg^-1·d^-1）, positive control group （ calcium disodium edentate plus procaine, im, 50 mg·kg- 1·d - 1 ） and model group. Seven treatment courses were carried out in the first three groups with every 4-d as one course and 4-d withdrawal period between every two courses. After 60 days, the change of lead in blood and kidney was observed by atomic absorption spectrometry,the apoptosis of kidney tissues was studied by TUNEL, the expression of Bcl-2 protein was detected by immunohistochemical methods and the expression of p53 was studied by Western Blotting. Results： Compared with the control group, the body weight, hemoglobin and the expression of Bcl-2 in the model group were decreased significantly （ P 〈 0.01 ） those in, and Pb in blood （0.990 s 0.443 ）μg·ml^-1, Pb in kidney （51.33±5.16）μg·ml^-1, the apoptosis of tubular epithelial ceil（4. 148±0.414） and the expression of p53 protein （ 1.868±0.139） were significantly higher （P 〈 0.05）. Compared with the those in model group, the body weight, hemoglobin and Bcl-2 in high-dose group were increased significantly（P 〈0.01 ）, and the blood lead level （0. 082±0.015）μg·ml^-1, the kidney lead level （6.38±0.97）μg·ml^-1, the apoptosis of tubular epithelial cell（ 1.412±0.109） and p53 protein expression（1.164±0.172） were significantly lower （ P 〈 0.05 ）. Conclusion： Lead may induce high expression of p53, low expression of Bcl-2 and promote the apoptosis of renal tubular epithelial cells