Jian K, Fok E, Cam M C, Sambandam N, Yao J, Rodrigues B
Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
Can J Physiol Pharmacol. 1996 Nov;74(11):1215-21.
Several studies have utilized the spontaneously hypertensive (SHR) diabetic rat to document the synergistic deleterious consequences of diabetes and hypertension on various organ systems. However, whether these effects are due entirely to the overlapping pathological states or partially result from a greater susceptibility of SHR rats to the diabetogenic effects of streptozotocin (STZ) is unclear. The present study was conducted to examine if strain-dependent variabilities in the STZ-induced diabetic state could also contribute to the pronounced complications previously observed in the SHR diabetic rat. To eliminate a possible modulating influence of severe hypertension on the beta-cytotoxic efficacy of STZ, SHR (SHRD), and Wistar (WisD) rats were injected with STZ (55 mg/kg i.v.) at 7-8 weeks of age, a time when there was no significant difference in systolic blood pressure between both stains. An oral glucose tolerance test was performed at 1 week following STZ and animals were killed at 2 weeks. Although both diabetic groups were equally hyperglycemic in the fed state, only SHRD rats had significantly elevated fasted glycemia at 1 week. Plasma insulin levels in the fed state or in response to oral glucose, as well as pancreatic insulin contents were diminished to a greater extent in the SHRD group relative to WisD. Fed plasma triglyceride (TG) levels were elevated only in the SHRD group, in association with a 4-fold reduction in basal circulating lipoprotein lipase (LPL) activity. However plasma TG clearance and LPL activity in response to i.v. heparin were not significantly altered in SHRD relative to SHR controls. The results in this study indicate that when evaluating the combined effects of diabetes and spontaneous hypertension, the STZ dose should be titrated to obtain an identical degree of diabetes in the SHR and a normotensive strain. In this regard, 45 (SHR) and 55 (Wistar) mg/kg STZ produced an identical milieu of diabetes.
多项研究利用自发性高血压（SHR）糖尿病大鼠来证明糖尿病和高血压对各种器官系统的协同有害影响。然而，这些影响是完全归因于重叠的病理状态，还是部分源于SHR大鼠对链脲佐菌素（STZ）致糖尿病作用的更高易感性，目前尚不清楚。本研究旨在检验STZ诱导的糖尿病状态下的品系依赖性差异是否也会导致先前在SHR糖尿病大鼠中观察到的明显并发症。为消除严重高血压对STZβ细胞毒性作用的可能调节影响，在7 - 8周龄时给SHR（SHRD）和Wistar（WisD）大鼠静脉注射STZ（55 mg/kg），此时两个品系的收缩压无显著差异。在注射STZ后1周进行口服葡萄糖耐量试验，并在2周时处死动物。尽管两个糖尿病组在进食状态下血糖均同样升高，但仅SHRD大鼠在1周时空腹血糖显著升高。相对于WisD组，SHRD组进食状态下或口服葡萄糖后的血浆胰岛素水平以及胰腺胰岛素含量降低程度更大。仅SHRD组进食状态下的血浆甘油三酯（TG）水平升高，同时基础循环脂蛋白脂肪酶（LPL）活性降低4倍。然而，相对于SHR对照组，SHRD组静脉注射肝素后的血浆TG清除率和LPL活性无显著改变。本研究结果表明，在评估糖尿病和自发性高血压的联合作用时，应调整STZ剂量以在SHR和正常血压品系中获得相同程度的糖尿病。在这方面，45（SHR）和55（Wistar）mg/kg的STZ产生了相同的糖尿病环境。
