血管加压素受体Ⅰ在实验性糖尿病大鼠肾脏和肝脏的调节

REGULATION OF RENAL AND HEPATIC VASOPRESSIN RECEPTORS IN EXPERIMENTAL DIABETIC RATS

本文利用链脲佐菌素诱导的实验性糖尿病大鼠,在糖尿病形成2周时分别测定血糖、肾小球滤过率(GFR)、血浆精氨酸血管加压素(AVP)、血钠及血浆渗透压,并用选择性AVP受体Ⅰ(V1)的放射配体^(125)I[d(CH_2)_5-Sarcosine^7]AVP对肾髓质膜和肝细胞膜V1受体进行结合分析。实验分三组:糖尿病组(D组)、胰岛素治疗组(T组)和对照组(C组)。结果表明,糖尿病形成2周时,各组血糖值为:D=37±7.5mmol/L;T=19±5.78mmol/L: C=7.63±0.59mmol/L。DT两组的GFR均增加,血浆AVP在D组明显高于对照组。膜受体结合试验显示:肾髓质膜V1受体最大结合容量(Bmax)在各组均无明显差异,解离常数(Kd值)D组大于T、C两组,肝细胞膜Bmax在T组增加,而Kd值在各组均未见改变。

Rats treated with streptozocin (STZ 55 mg, iv, tail vein) induced diabetes then divided into 2 groups: diabetes (D), insulin-treated (T), other rats gaven vehicle as control (0). Two weeks later, plasma glucose, glomerular filtration rate (GFR) and plasma argirine vasopressin (AVP) were measured. 125I [d(CH2)5-Sarcosine7] AVP, a selective vasopressin V1 receptor antagonist was used as a redioligand in renal medulla and hepatic membrane binding stadies. GFR was increased in D and T groups (D = l6.98±2.56ml/min-1·kg-1, T= 15.49±0.99 ml/min-1·kg-1, C = 12.30±0.69ml/min-1·kg-1). AVP cor centration was elevated in D group (D = 8.22±0.85pg/ml, T = 7.01±0.42pg/ml, C = 6.55±0.82pg/ml). Binding studies showed that the kidney medullary membrane Bmax was unchanged in 8 groups but the Kd value was significantly higher in the D group than in the other groups(D = 0.89±0.06. T = 0.50±0.07, 0 = 0.50±0.08); hepatic membrane Bmax was increased in the T group (D = 85.20±16.5, T= 120±8.0, 0 = 98.0±13.0). We conclude that a lowered affinity of V1 receptors in diabetic rat is probably a factor causing increase in GFR. and a different mode of regulation of V1 receptors in the kidney and the liver was shown in this study.