Bunchman T E, Mauer S M, Kim Y
Department of Pediatric Nephrology, University of Minnesota, Minneapolis.
Diabetes. 1990 Jan;39(1):83-6. doi: 10.2337/diacare.39.1.83.
The effect of cyclosporin (CsA) on the endotoxin-induced generalized Shwartzman reaction (GSR) was studied in diabetic and nondiabetic rats. After 4.5 wk of diabetes, CsA (20 mg/kg) or intralipid as a control substance was given intraperitoneally daily for 10 days. Next, diabetic rats were given either high-dose (2 mg/kg or low-dose (0.1 mg/kg) endotoxin (Escherichia coli 026:B6 lipopolysaccharide B) as a single injection. The rats were killed at intervals of 1, 4, 8, and 24 h. No significant glomerular thrombi were seen in the nondiabetic control animals, whereas the severity of glomerular thrombi in the diabetic animals was dependent on the presence or absence of CsA, endotoxin dose, and degree of glycemic control. In the diabetic rats, glomerular thrombi occurred maximally at 4 h but were no longer present at 24 h. The CsA/high-dose-endotoxin rats had fewer glomerular thrombi than rats receiving the intralipid/high-dose endotoxin, but this difference was not statistically significant. The CsA/low-dose-endotoxin rats had increased glomerular thrombi compared with the intralipid/low-dose-endotoxin rats (P less than 0.01). Insulin treatment reduced the glomerular capillary thrombi in the CsA/low-dose-endotoxin diabetic animals. Thus, CsA aggravates the GSR with low-dose endotoxin but has no significant effect when high-dose endotoxin is given. Improved glycemic control reduces the GSR in CsA-treated rats. Thus, the interrelationships of diabetes, endotoxin, and CsA on the GSR are complex, and the pathogenesis of these events is unclear.
在糖尿病和非糖尿病大鼠中研究了环孢素（CsA）对内毒素诱导的全身性施瓦茨曼反应（GSR）的影响。糖尿病造模4.5周后，每天腹腔注射CsA（20mg/kg）或作为对照物质的脂肪乳剂，持续10天。接下来，给糖尿病大鼠单次注射高剂量（2mg/kg）或低剂量（0.1mg/kg）内毒素（大肠杆菌026:B6脂多糖B）。在1、4、8和24小时的间隔时间处死大鼠。在非糖尿病对照动物中未观察到明显的肾小球血栓形成，而糖尿病动物中肾小球血栓形成的严重程度取决于CsA的存在与否、内毒素剂量和血糖控制程度。在糖尿病大鼠中，肾小球血栓在4小时时出现最多，但在24小时时不再存在。CsA/高剂量内毒素组大鼠的肾小球血栓比接受脂肪乳剂/高剂量内毒素的大鼠少，但这种差异无统计学意义。与脂肪乳剂/低剂量内毒素组大鼠相比，CsA/低剂量内毒素组大鼠的肾小球血栓增加（P<0.01）。胰岛素治疗减少了CsA/低剂量内毒素糖尿病动物的肾小球毛细血管血栓。因此，CsA加重低剂量内毒素诱导的GSR，但给予高剂量内毒素时无显著影响。改善血糖控制可降低CsA处理大鼠的GSR。因此，糖尿病、内毒素和CsA对GSR的相互关系很复杂，这些事件的发病机制尚不清楚。
