兔血清对氧磷酶-1对于敌敌畏所致大鼠肾损伤的保护作用

The protective effect of rabbit serum paraoxonase-1 on the renal injury induced by dichlorvos in rats

目的探讨家兔血清对氧磷酶-1（paraoxonase-1，PON-1）对敌敌畏所导致的大鼠肾损伤的保护作用。方法将30只SD大鼠随机（随机数字法）分成5组，每组6只。正常组（A组）、染毒组（B组）、PON．1预处理组（C组）、传统阿托品加解磷定治疗组（D组）、联合治疗组（E组）。A组予大鼠腹腔注射与敌敌畏同等体积的生理盐水；B、C、D、E组均予大鼠腹腔注射敌敌畏9ms／kg。C、E组在腹腔注射敌敌畏前30min，予大鼠尾静脉注射PON-14500U／kg。C、D组注射敌敌畏后予大鼠碘解磷定45mS／kg，阿托品10mg／kg腹腔注射。采用苦味酸比色法测定肌酐（cr）及脲酶法测定尿素氮（BUN）的活性，采用ELISA法检测血清胱抑素-C（Cys—C）的数值，尿液的肾损伤分子-1（KIM-1）及N-乙酰-B-D-葡萄糖苷酶（NAG）的数值。采用光镜检查大鼠肾脏超微结构的改变。比较各组之间相关指标的差异。结果B组肌酐、尿素氮等肾功能指标较其他组升高，差异有统计学意义（P〈0．05）。B组和D组的Cys—C，KIM-1，NAG较A、C、E组均有明显升高，差异有统计学意义（P〈0．01），B组和D组之间、A、C、E组间的差异无统计学意义（P〉0．05）。B组大鼠肾脏炎性细胞广泛浸润，细胞充血水肿严重，管腔闭塞，刷状缘消失，无明确的小管结构；D组肾脏仍然出现小管细胞变性水肿，炎性细胞浸润，较染毒组有所减轻，可见明确小管结构，管腔未完全闭塞，并且以远曲小管病变最为严重。C、E组仅有轻度充血、水肿，无明显的细胞变性坏死。A组肾小管上皮结构清楚，可见刷状缘，管腔内无管型及坏死的细胞碎片。结论兔血清PON-1对敌敌畏造成的大鼠。肾损伤有保护作用。

Objective To assess the protective effect of rabbit serum paraoxonase-1 （PON-1） on renal injury induced by dichlorvos in rats. Methods Totally 30 healthy S-D rats were randomly divided into 5 groups ： control group （ group A, n = 6）, exposure group （ group B, n = 6）, PON-1 pretreatment group （ group C, n = 6 ）, traditional atropine, pralidoxime treatment group （ group D, n = 6 ） and combination therapy group （ group E, n = 6）. The rats of group A were given normal saline in equal volume of dichlorvos injected into abdominal cavity to make a false model of dichlorvos poisoning. In rats of groups B, C, D and E, 9 mg/kg dichlorvos was administered. In rats of groups C and E, PON-1 4 500 units/kg was injected into vein of the tails half, an hour before dichlorvos administration. After dichlorvos exposure, rats in group D and E were treated with 45 mg/kg iodoprofen and 10 mg/kg atropine by intraperitoneal injection. The activity of blood urea nitrogen （BUN） was assayed with urease. Serum creatinine （Cr） were measured by picric acid colorimetry. Serum Cys-C, KIM-1 and NAG in urine were determined by ELISA. Ultrastructural changes in renal tissues of rats were examined by light microscopy. The differences in laboratory findings between groups were compared. Results The creatinine level in group B was significantly higher than that in other groups （P 〈 0.05）. The levels of Cys-C, KIM-1 and NAG in group B and group D were significantly higher than those in group A （ P 〈 0. 01 ）. But there were no significant differences in above biomarkers among group C, group E and group A. There were no significant differences in above biomarkers between group B and group D. In group B, inflammatory cells infiltrated extensively in renal tissues and, the renal cells were congested and edematous, the lumen was obliterated and the border of the brush disappeared. The tubular structures were not clearly distinct found in group B, but edema and inflammatory cell infiltration with lesser degree were found in group D than those in dichlorvos exposure groups. The clearly distinct structure of the tube without completely occluded lumen in group D, and the most serious lesions were found in distal convoluted tubules. In group C, and group E, there were only mild congestion and edema without significant cell degeneration and necrosis. In group A, the structure of renal tubular epithelium was clearly distinct with brush-shaped margin, and without tubular or necrotic cell debris in the lumen. Conclusion The rabbit serum PON-1 can protect the renal tissue of rats after dichlorvos exposure.