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糖尿病小鼠中的克氏锥虫感染。

Trypanosoma cruzi infection in diabetic mice.

作者信息

Tanowitz H B, Amole B, Hewlett D, Wittner M

机构信息

Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461.

出版信息

Trans R Soc Trop Med Hyg. 1988;82(1):90-3.

PMID:3140447
Abstract

The course of infection due to Trypanosoma cruzi (Brazil strain) was examined in mutant and streptozotocin (STZ)-induced diabetic mice. Mutant diabetic mice (+db/+db) are obese, have elevated blood glucose levels, normal insulin levels and impaired cell mediated immunity (CMI). Their littermates (m+/m+, m+/+db) are of normal weight, normoglycaemic and immunocompetent. Infected +db/+db mice died within 20-25 d after infection (AI) with a mean peak parasitaemia of 6 X 10(6) trypomastigotes/ml accompanied by heavy tissue parasitism. The nondiabetic littermates had low, transient, parasitaemia, no tissue parasitism, and 100% survival. Immune mouse serum (IMS) was given to infected +db/+db mice thrice weekly beginning on day 1 AI. During IMS treatment, parasitaemia remained significantly lower than in untreated mice. However, when IMS treatment was discontinued parasitaemia rose and mortality ensued. To examine the effects of hyperglycaemia in the absence of other variables such as genetics or CMI, T. cruzi infection was studied in STZ-induced diabetic mice. Normal C57BL/6 mice, resistant to infection with the Brazil strain, exhibited low transient parasitaemia and no mortality. In contrast, STZ-induced hyperglycaemic C57BL/6 mice developed high parasitaemia and 100% mortality by day 40 AI. When these hyperglycaemic mice were treated with insulin continuously by pump, their blood glucose levels returned to normal but parasitaemia and mortality were unchanged. These data indicate that hyperglycaemia significantly increases parasitaemia and mortality in mice infected with T. cruzi.

摘要

在突变型和链脲佐菌素(STZ)诱导的糖尿病小鼠中研究了克氏锥虫(巴西株)的感染过程。突变型糖尿病小鼠(+db/+db)肥胖,血糖水平升高,胰岛素水平正常,细胞介导免疫(CMI)受损。它们的同窝小鼠(m+/m+,m+/+db)体重正常,血糖正常,免疫功能正常。感染的+db/+db小鼠在感染(AI)后20 - 25天内死亡,平均峰值寄生虫血症为6×10⁶锥鞭毛体/ml,伴有严重的组织寄生。非糖尿病同窝小鼠的寄生虫血症低且短暂,无组织寄生,存活率为100%。从AI第1天开始,每周三次给感染的+db/+db小鼠注射免疫小鼠血清(IMS)。在IMS治疗期间,寄生虫血症仍显著低于未治疗的小鼠。然而,当停止IMS治疗时,寄生虫血症上升并导致死亡。为了在没有遗传学或CMI等其他变量的情况下研究高血糖的影响,在STZ诱导的糖尿病小鼠中研究了克氏锥虫感染。对巴西株感染有抵抗力的正常C57BL/6小鼠表现出低且短暂的寄生虫血症,无死亡。相比之下,STZ诱导的高血糖C57BL/6小鼠在AI第40天时出现高寄生虫血症和100%死亡。当这些高血糖小鼠通过泵持续注射胰岛素时,它们的血糖水平恢复正常,但寄生虫血症和死亡率未改变。这些数据表明,高血糖显著增加了感染克氏锥虫小鼠的寄生虫血症和死亡率。

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