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抗肿瘤坏死因子-α抗体对先兆子痫Wistar孕鼠某些肾功能及血管调节因子的潜在作用

The potential role of anti tumor necrosis factor-alpha antibodies on some renal functions and vasoregulatory factors in preeclamptic pregnant Wistar rats.

作者信息

Gad Hayam I

机构信息

Physiology Department, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia.

出版信息

Saudi Med J. 2013 May;34(5):490-6.

Abstract

OBJECTIVE

To investigate the potential role of anti-tumor necrosis factor-alpha (TNF-alpha) antibodies on some renal functions and release of vasoregulatory peptides using nitric oxide synthase deprived pregnant rats.

METHODS

This study was carried out at King Khalid University Hospital, King Saud University, Riyadh, Kingdom of Saudi Arabia from December 2011 to November 2012. Forty female Wistar rats were divided into 4 groups (10 rats each); Group I - included virgin non-pregnant rats. Group II - included pregnant rats that received saline, Group III - received NG-nitro-L-arginine methyl ester (L-NAME), and Group IV - received both L-NAME and anti TNF-alpha antibodies. Mean arterial blood pressure, urine volume, creatinine clearance and 24 hours urinary albumin excretion were measured on day 20 of gestation. Blood samples were taken on day 20 of gestation for measurement of plasma endothelin-1 (ET-1), angiotensin II (Ag II) and serum levels of total nitric oxide (NO) products, interleukin-6 (IL-6) and soluble vascular cell adhesion molecule (sVCAM-1). Viable pups were also weighed.

RESULTS

Anti TNF-alpha antibodies reversed hypertension, improved renal function, decreased release of vasoactive substances and increased pup weight.

CONCLUSION

Preeclampsia is associated with disturbed renal function, overproduction of cytokines and vasoregulatory factors, and fetal growth restriction. Treatment of pregnant rats with anti TNF-alpha antibodies, restored urine volume, creatinine clearance, plasma ET-1, serum IL-6 and sVCAM-1 to normal levels. Hence, anti TNF-alpha antibodies may have beneficial effects in preeclampsia. Additional studies are warranted to confirm these results.

摘要

目的

利用一氧化氮合酶缺乏的妊娠大鼠,研究抗肿瘤坏死因子-α(TNF-α)抗体对某些肾功能及血管调节肽释放的潜在作用。

方法

本研究于2011年12月至2012年11月在沙特阿拉伯利雅得国王沙特大学国王哈立德大学医院进行。40只雌性Wistar大鼠分为4组(每组10只);第一组 - 包括未孕处女大鼠。第二组 - 包括接受生理盐水的妊娠大鼠,第三组 - 接受NG-硝基-L-精氨酸甲酯(L-NAME),第四组 - 接受L-NAME和抗TNF-α抗体。在妊娠第20天测量平均动脉血压、尿量、肌酐清除率和24小时尿白蛋白排泄量。在妊娠第20天采集血样,用于测量血浆内皮素-1(ET-1)、血管紧张素II(Ag II)以及总一氧化氮(NO)产物、白细胞介素-6(IL-6)和可溶性血管细胞粘附分子(sVCAM-1)的血清水平。还对存活的幼崽进行称重。

结果

抗TNF-α抗体可逆转高血压、改善肾功能、减少血管活性物质的释放并增加幼崽体重。

结论

子痫前期与肾功能紊乱、细胞因子和血管调节因子过度产生以及胎儿生长受限有关。用抗TNF-α抗体治疗妊娠大鼠,可使尿量、肌酐清除率、血浆ET-1、血清IL-6和sVCAM-1恢复至正常水平。因此,抗TNF-α抗体可能对子痫前期有有益作用。需要进一步研究来证实这些结果。

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