孕期铅暴露对生长发育期大鼠肾功能及Claudin-2的影响

目的 通过建立孕期染铅模型检测出生后SD仔鼠肾功能的改变及紧密连接蛋白Claudin-2的改变,阐明孕期铅暴露对SD仔鼠肾功能的影响.方法 SD孕鼠通过饮用50 mg/L,100 mg/L醋酸铅（PbC4H6O4＆#183;3H2O）的方法建立模型.仔鼠出生后6周检测血液中肌酐（Cr）、尿素氮（BUN）和胱抑素C（CYS-C）水平的变化,肾组织形态及Claudin-2的改变,探讨孕期铅暴露对SD仔鼠肾功能的影响.结果 血铅结果显示,低剂量组仔鼠血铅水平（146.28±15.10 μg/L）与高剂量组仔鼠血铅水平（188.03±18.58μg/L）较对照组明显升高,差异有统计学意义（F=5.22,P＜0.01）,且低剂量组与高剂量组之间,差异有统计学意义（F=5.53,P＜0.05）,说明模型建立成功.染铅SD仔鼠血肌酐（9.31±1.98 μmol/L,F=5.89,P＜0.01）,尿素氮（89.73±14.45 mmol/L,F=5.01,P＜0.01）和CYS-C（0.37±0.04mg/L,F=6.96,P＜0.01）水平升高,病理结果显示：染铅组仔鼠肾小球轻度肿大,伴炎性细胞浸润;部分肾小管上皮细胞变形、坏死,部分管腔内有管型.免疫荧光结果显示,染铅组仔鼠Claudin-2表达下降,连续性被破坏.结论 孕期铅暴露能引起生长发育期大鼠的肾功能不全,并且铅暴露可以降低肾小管Claudin-2的表达.

Effect of Gestational Lead Exposure on Renal Functions and the Expression of Claudin-2 in the Growing Rats

Objective By investigating the renal functions and the change of tight junction protein Claudin-2 after gestationallead exposure,try to clarify the effect of gestational lead exposure on the growing rats＇ renal functions. Methods Femalepregnant spraque-dawley（SD） rats were divided into low dose group and： high dose group by drinking 50 mg/L or 100 mg/Llead acetate dissolved by distilled water,with control group drinking distill water. The newborn rats were used to study theeffect of lead on renal functions. Blood creatine （Cr）, serum urea （BUN）, cystatin C （CYS-C） and pathology tests were usedto examine renal functions. Immunochemistry was used to observe the change of Claudin-2. Results The results of bloodlead showed that low dose group （146.28±15.10 rig/L） and high dose group （188.03±18.58 μg/L） had much more leadthan the control group （F= 5.22, P〈0. 01）, which suggested that our gestational lead model was successful. The level of Cr（9.31±1.98 μmol/L,F=5.89,P〈0.01）,BUN （89.73±14.45 mmol/L,F=5.01,P〈0.01） and CYS-C （0.37±0.04mg/L,F=6.96,P〈0.01） were significantly increased in postnatal rats exposed to lead compared with the control （P〈0.05）. Pathology results showed that lead exposure induced mild damage in glomerulus and heavy injury in renal tubules.Immunochemistry showed that the expression of Claudin-2 was reduced by lead exposure. Conclusion Gestational lead expo-sure causes the deficiency of renal function and decreasing expression of Claudin-2 in the growing rats.