糖尿病妊娠大鼠模型的心血管和肾脏特征以及对急性容量扩张的反应

Cardiovascular and renal characteristics, and responses to acute volume expansion of a rat model of diabetic pregnancy.

作者信息

Tang Daiyi, Yu Tianzheng, Khraibi Ali A

机构信息

Department of Physiological Sciences, Eastern Virginia Medical School, P.O. Box 1980, Norfolk, VA 23501-1980, USA.

出版信息

Life Sci. 2004 Apr 23;74(23):2909-18. doi: 10.1016/j.lfs.2003.11.005.

DOI:10.1016/j.lfs.2003.11.005

PMID:15050428

Abstract

The objective of this study was to characterize the cardiovascular and renal alterations that occur during diabetic pregnancy, and to evaluate the effect of insulin treatment in 12-14 days pregnant diabetic rats. Four groups of female Sprague Dawley rats were studied: virgin control group (NP), pregnant control group (CP), diabetic pregnant group (DP), and diabetic pregnant group with insulin treatment (DPI). Systolic arterial pressure (SAP) was increased on day 12, whereas heart rate (HR) decreased starting with day 3 in DP group of rats. DP rats exhibited marked renal hypertrophy with greater kidney weight (wt) and kidney wt/body wt ratio. Insulin treatment normalized blood glucose (BG) concentration, SAP and HR, and prevented the increase in kidney wt/body wt ratio in DPI rats. At the time of the terminal acute experiment, acute saline volume expansion (VE, 5% body wt/30 min) significantly increased renal interstitial hydrostatic pressure (RIHP), urinary sodium excretion (U(Na)V) and urine flow rate (V) in all groups, but the increases (Delta) were significantly attenuated in both CP (1.7 +/- 0.2mmHg, 12.0 +/- 1.5 microEq.min(-1).g kidney wt(-1) and 76.2 +/- 10.9 microl.min(-1).g kidney wt(-1) for DeltaRIHP, DeltaU(Na)V and DeltaV respectively) and DP (1.3 +/- 0.1 mmHg, 6.8 +/- 1.8 microEq.min(-1).g kidney wt(-1) and 32.3 +/- 9.3 microl.min(-1).g kidney wt(-1) for DeltaRIHP, DeltaU(Na)V and DeltaV respectively) group of rats as compared to NP (4.0 +/- 0.6 mmHg, 21.6 +/- 1.4 microEq.min(-1).g kidney wt(-1)and 136.8 +/- 10.5 microl.min(-1).g kidney wt(-1) for DeltaRIHP, DeltaU(Na)V and DeltaV respectively) group of rats. Although RIHP response to VE was similar in DP and CP group of rats, the natriuretic and diuretic responses to VE were significantly lower in DP as compared to CP group of rats. Insulin treatment had no effect on RIHP response (DeltaRIHP = 1.5 +/- 0.3 mmHg), but restored most of the natriuretic (DeltaU(Na)V = 15.7 +/- 2.9 microEq.min(-1).g kidney wt(-1)) and diuretic (DeltaV = 100.2 +/- 19.3 microl.min(-1).g kidney wt(-1)) responses to VE in DPI as compared with CP group of rats. These data suggest that with VE, the restoration of the increase in U(Na)V and V with insulin treatment in diabetic pregnant rats is not mediated by changes in RIHP.

摘要

本研究的目的是描述糖尿病妊娠期间发生的心血管和肾脏改变，并评估胰岛素治疗对妊娠12 - 14天的糖尿病大鼠的影响。研究了四组雌性斯普拉格 - 道利大鼠：未孕对照组（NP）、妊娠对照组（CP）、糖尿病妊娠组（DP）和胰岛素治疗的糖尿病妊娠组（DPI）。在第12天，糖尿病大鼠组（DP）的收缩动脉压（SAP）升高，而心率（HR）从第3天开始下降。DP大鼠表现出明显的肾脏肥大，肾脏重量（wt）和肾脏重量/体重比增加。胰岛素治疗使血糖（BG）浓度、SAP和HR恢复正常，并防止了DPI大鼠肾脏重量/体重比的增加。在终末急性实验时，急性生理盐水容量扩张（VE，5%体重/30分钟）使所有组的肾间质静水压（RIHP）、尿钠排泄（U(Na)V）和尿流率（V）显著增加，但与未孕对照组（NP）（RIHP、U(Na)V和V的变化量分别为4.0±0.6 mmHg、21.6±1.4微当量·分钟⁻¹·克肾脏重量⁻¹和136.8±10.5微升·分钟⁻¹·克肾脏重量⁻¹）相比，妊娠对照组（CP）（RIHP、U(Na)V和V的变化量分别为±1.7 0.2 mmHg、12.0±1.5微当量·分钟⁻¹·克肾脏重量⁻¹和76.2±10.9微升·分钟⁻¹·克肾脏重量⁻¹）和糖尿病妊娠组（DP）（RIHP、U(Na)V和V的变化量分别为1.3±0.1 mmHg、6.8±1.8微当量·分钟⁻¹·克肾脏重量⁻¹和32.3±9.3微升·分钟⁻¹·克肾脏重量⁻¹）大鼠的增加量（Δ）显著减弱。尽管DP组和CP组大鼠对VE的RIHP反应相似，但与CP组大鼠相比，DP组大鼠对VE的利钠和利尿反应显著降低。胰岛素治疗对RIHP反应（ΔRIHP = 1.5±0.3 mmHg）无影响，但与CP组大鼠相比，恢复了DPI组大鼠对VE的大部分利钠（ΔU(Na)V = 15.7±2.9微当量·分钟⁻¹·克肾脏重量⁻¹）和利尿（ΔV = 100.2±19.3微升·分钟⁻¹·克肾脏重量⁻¹）反应。这些数据表明，对于容量扩张，糖尿病妊娠大鼠胰岛素治疗后U(Na)V和V增加的恢复不是由RIHP的变化介导的。