Studies on the cause of HELLP syndrome

HELLP综合征病因研究

• 批准号: 05454443
• 负责人: TERAO Tosihiko
• 金额: $ 4.22万
• 依托单位: Hamamatsu University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05454443/
• 关键词: HELLP syndrome; sympathetic ganglion; vasospasm; endothelin; cytokines; 腹腔神経節; 動物モデル; Vaso spasm; 妊娠中毒症

Aim : To determine the role of vasospasm of celiac artery, we have also performed several animal and clinical experiments. Materials and Methods : Immunostaining with anti TNF-alpha, anti neutrophil elastase, anti IL-1, anti IL-8 antibodies was done on hepatic tissues obtained from eclamptic and preeclamptic HELLP syndrome patients to understand the role of neutrophil or some cytokines in tissue damage in such disease. ET-1 was injected in pregnant and nonpregnant rabbits and their different blood parameters were investigated and analyzed. Endotoxin, potassium chloride, and saline solution were superposed on the celiac ganglion in pregnant or non-pregnant rats. Endotoxin was also superposed on bifurcation of the abdominal aorta. The blood pressure, proteinuria and various blood parameters were measured. Results : Periportal hemorrhage and ischemic necrosis with marked infiltration of neutrophils in liver tissues were found in HELLP syndrome cases. Those tissues were stained strongly to TNF-alpha and neutrophil elastase and moderately with polyclonal IL-1beta and IL-8 antibodies indicating that cytokine production induced by vasospasms occurred. Vasoconstriction of the hepatic artery following a bolus injection of 0.25 nmol/kg of ET-1 into the celiac artery occurred in rabbits. HELLP syndrome like biochemical parameters were obtained after the ET-1 injections and stimulation of celiac ganglions. Histological examination of liver tissues treated with injections of endothelin and stimulation of celiac ganglions showed varying degrees of ischemic necrosis of hepatocytes similar to human HELLP syndrome. Conclusion : This study suggests that injections of endothelin-1 and an exogenous stimulation of the celiac ganglion causes an increase in the blood pressure and liver ischemia, resulting in HELLP syndrome-like disease in pregnant and non-pregnant rats. We suggest that ET-1 and abdominal sympathetic nerve might play a causative role in HELLP syndrome.

目的：为了确定腹腔动脉痉挛的作用，我们还进行了一些动物和临床实验。材料与方法：用抗TNF-α、抗中性粒细胞弹性蛋白酶、抗IL-1、抗IL-8抗体对从子痫和子痫前期HELLP综合征患者获得的肝组织进行免疫染色，以了解中性粒细胞或某些细胞因子在此类疾病的组织损伤中的作用。给孕兔和非孕兔注射ET-1，观察并分析其血液学指标的变化。将内毒素、氯化钾和生理盐水叠加在妊娠或非妊娠大鼠的腹腔神经节上。内毒素也叠加在腹主动脉分叉处。测定血压、尿蛋白及各项血液指标。结果：HELLP综合征表现为门静脉周围出血、缺血性坏死，肝组织中性粒细胞浸润明显。这些组织被TNF-α和中性粒细胞弹性蛋白酶强烈染色，被多克隆IL-1 β和IL-8抗体中度染色，表明发生了血管痉挛诱导的细胞因子产生。家兔腹腔动脉注射0.25nmol/kg ET-1后，肝动脉发生收缩。注射ET-1和刺激腹腔神经节后，获得HELLP综合征样生化指标。注射内皮素和刺激腹腔神经节处理的肝组织的组织学检查显示类似于人类HELLP综合征的不同程度的肝细胞缺血性坏死。结论：这项研究表明，注射内皮素-1和腹腔神经节的外源性刺激导致血压升高和肝脏缺血，导致妊娠和非妊娠大鼠的HELLP综合征样疾病。提示ET-1和腹交感神经可能在HELLP综合征中起一定作用。

项目成果

Halim A.: "Activated neutrophil by endothelin-l caused tissue damage in human umbilical cord" Thromb.Res.77. 321-327 (1995)

Halim A.：“内皮素-1 激活的中性粒细胞导致人脐带组织损伤”Thromb.Res.77。

Halim A., Kanayama N., El Maradny E., Machara K., and Terao T: "Coagulation in vivo microcirculation and in vitro caused by endothelin-1." Thromb.Res. 72. 203-209 (1993)

Halim A.、Kanayama N.、El Maradny E.、Machara K. 和 Terao T：“内皮素 1 引起的体内微循环和体外凝血。”

Halim A., Bhuiyan A.B., Azim F.A., Khatun S., Kanayama N., El Maradny E., Machara K., Kobayashi H., and Terao T.: "Blood coagulation and fibrinolysis in eclamptic paticnts and thcir correlation with the clinical signs." Gynecol. Obstet. Invest.39. 97-102

Halim A.、Bhuiyan A.B.、Azim F.A.、Khatun S.、Kanayama N.、El Maradny E.、Machara K.、Kobayashi H. 和 Terao T.：“子痫患者的凝血和纤溶及其与临床的相关性

金山 尚裕: "HELLP症候群の病態と解析" 腎と透析. 39. 748-752 (1995)

Naohiro Kanayama：“HELLP 综合征的病理学和分析”《肾脏与透析》39. 748-752 (1995)。

Halim A.: "Coagulation in vivo microcirculation and in vitro caused by endothelin-1" Thromb.Res.72. 203-209 (1993)

Halim A.：“内皮素-1 引起的体内微循环和体外凝血”Thromb.Res.72。