心钠素两种不同受体mRNA在阿霉素诱导的肾病综合征大鼠肾脏的表达

ATRIAL NATRIURETIC PEPTIDE RECEPTORS mRNA EXPRESSION IN ADRIAMYCIN INDUCED NEPHROTIC RAT KIDNEY

目的：在阿霉素诱导的肾病综合征大鼠动物模型探讨肾病水肿发病机理。方法：观察阿霉素诱导的肾病综合征大鼠模型扩容利尿反应及心钠素（ＡＮＰ）两种受体的表达。结果：肾病大鼠对扩容利尿的反应较正常对照组明显下降（Ｐ＜０．０１）。虽然两组大鼠在扩容时血浆心钠素上升幅度相似，但其尿中ＡＮＰ第二信使ｃＧＭＰ的排泄（ＵｃＧＭＰＶ）在肾病组比正常对照组明显下降（５．８５±２．６～３１．４±７．５ｖｓ６．０２±３．０～９８．４５±１６．８ｐｍｏｌ／ｍｉｎ，Ｐ＜０．０１）。Ｎｏｒｔｈｅｒｎ杂交显示，两组大鼠肾脏ＡＮＰ－Ａ受体ｍＲＮＡ表达相似，但肾病组大鼠肾脏ＡＮＰ－Ｃ受体ｍＲＮＡ表达较正常对照组明显升高（Ａ×ａｒｅａ１ｖｓ０．３２，Ｐ＜０．０１）。结论：肾病综合征水钠潴留可能与其肾脏ＡＮＰ－Ｃ受体高表达有关。

OBJECTIVE It has been known that nephrotic patients have atrial natriuretic peptide(ANP) resistance. Up to now, the mechanism for ANP resistance is still unclear. To explore the mechanism, the effects of volume expansion and the role of ANP A/C receptors on nephrotic edema are investigated in adriamycin induced nephrotic rats.METHODOLOGY Male SD rats, body weight about 200g, were used. Twelve nephrotic rats were induced by administrating adriamycin at 6mg/100g through tail vein injection. And twelve normal rats were set as the control. At the end of the third week of experiment, all the animals were treated with infusion of 2% body weight normal saline, and the inlune clearance (GFR), plasma ANP concentration, urinary cGMP excretion were determined before and after volume expansion. At the same time, the expression of ANP A/C receptors mRNA in rat renal tissue was investigated in the sacrificed animals from these two groups.RESULTS The nephrotic rats had a blunted natriuretic response to volume expansion as compared to the normal control rats(P<001). Although a similar increased plasma ANP concentration after volume expansion were found in the two groups of rats, the nephrotic rats had a reduced rate of UcGMP V after saline infusion as compared to the controls(585±26 to 314±75 vs 602±30 to 9845±168, P<001). Northern blot showed that expression of ANPC receptor mRNA was significantly increased in nephrotic rats(A×area: 1 vs 032,P<001) while no difference was found in ANPA receptor mRNA expression between the two groups.CONCLUSION Nephrotic edema may be related to the high expression of ANPC receptor in nephrotic state.