乌司他丁缓解子痫前期大鼠高血压、蛋白尿和炎症反应的实验研究

doi:10.11958/20220357

天津医药 ›› 2022, Vol. 50 ›› Issue (9): 943-947.doi: 10.11958/20220357

乌司他丁缓解子痫前期大鼠高血压、蛋白尿和炎症反应的实验研究

董彦(), 崔剑, 张丽, 郎楠, 王建波, 于志强()

天津市中心妇产科医院麻醉科（邮编300100）

收稿日期:2022-03-15 修回日期:2022-05-25 出版日期:2022-09-15 发布日期:2022-09-05
通讯作者: 于志强 E-mail:18622119686@163.com;120yuzhi@163.com
作者简介:董彦（1975）,女,主治医师,主要从事妇产科麻醉与危重症方面研究。E-mail： 18622119686@163.com
基金资助:
天津市人类发育与生殖调控重点实验室资助项目(2019HX01)

Effects of UTI on alleviating hypertension, proteinuria and inflammatory response in PE rats

DONG Yan(), CUI Jian, ZHANG Li, LANG Nan, WANG Jianbo, YU Zhiqiang()

Department of Anesthesiology, Tianjin Central Hospital of Gynecology and Obstetrics, Tianjin 300100, China

Received:2022-03-15 Revised:2022-05-25 Published:2022-09-15 Online:2022-09-05
Contact: YU Zhiqiang E-mail:18622119686@163.com;120yuzhi@163.com

董彦, 崔剑, 张丽, 郎楠, 王建波, 于志强. 乌司他丁缓解子痫前期大鼠高血压、蛋白尿和炎症反应的实验研究[J]. 天津医药, 2022, 50(9): 943-947.

DONG Yan, CUI Jian, ZHANG Li, LANG Nan, WANG Jianbo, YU Zhiqiang. Effects of UTI on alleviating hypertension, proteinuria and inflammatory response in PE rats[J]. Tianjin Medical Journal, 2022, 50(9): 943-947.

摘要/Abstract

摘要：

目的探讨乌司他丁（UTI）用于缓解子痫前期（PE）大鼠高血压、蛋白尿和炎症反应的可行性。方法将56只孕12 d（G12）的SD大鼠随机分为对照组（C组,腹腔注射生理盐水）、PE组（腹腔注射左旋硝基精氨酸甲酯200 mg·kg^-1·d^-1建立PE大鼠模型）、PE+U₁组（PE大鼠腹腔注射UTI 5 000 IU·kg^-1·d^-1）和PE+U₂组（PE大鼠腹腔注射UTI 10 000 IU·kg^-1·d^-1）。测量各组大鼠G12、G13、G15、G17、G19收缩压（SBP）,G12、G19的24 h尿蛋白,G20血浆和胎盘中肿瘤坏死因子-α（TNF-α）、白细胞介素6（IL-6）、血管性假血友病因子（vWF）和胎盘生长因子（PLGF）水平。结果与C组相比,PE、PE+U₁、PE+U₂组在G13、G15、G17、G19时的SBP和G19时的尿蛋白水平均升高,UTI可降低PE大鼠的SBP和尿蛋白含量,PE+U₂组减少尿蛋白的作用更明显（P<0.05）。与C组相比,PE、PE+U₁组在G20时血浆和胎盘中TNF-α和IL-6水平升高,PE+U₂组仅胎盘中TNF-α水平升高;UTI可降低PE大鼠血浆和胎盘中TNF-α和IL-6水平,PE+U₂组降低血浆、胎盘中TNF-α水平和胎盘中IL-6水平的作用更明显（P<0.05）。与C组相比,PE、PE+U₁组在G20时血浆和胎盘中PLGF水平降低、vWF水平升高,PE+U₂组仅血浆和胎盘中vWF水平升高;UTI可提升PE大鼠血浆和胎盘中PLGF水平、降低vWF水平,PE+U₂组降低血浆和胎盘中vWF水平的作用更明显（P<0.05）。结论 UTI可抑制PE大鼠血浆和胎盘中的炎症反应,减轻血管内皮损伤,有效缓解PE大鼠的高血压和蛋白尿;且10 000 IU·kg^-1·d^-1的治疗效果优于5 000 IU·kg^-1·d^-1。

关键词: 先兆子痫, 高血压,妊娠性, 蛋白尿, 炎症反应, 乌司他丁

Abstract:

Objective To explore the effectiveness and feasibility of ulinastatin (UTI) in the treatment of pre-eclampsia (PE) rats. Methods Fifty-six SD rats at 12 days of gestation (G12) were randomly divided into 4 groups: the control group (group C, intraperitoneal injection of normal saline), the PE group (intraperitoneal injection of L-NAME 200 mg/kg), the PE+U₁ group (PE rats injected with UTI 5 000 IU·kg^-1·d^-1) and the PE+U₂ group (PE rats injected with UTI 10 000 IU·kg^-1·d^-1). The systolic blood pressure (SBP) was measured on G12, G13, G15, G17 and G19, and urinary protein in 24 hours was measured on G12 and G19. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), von Willebrand factor (vWF) and placental growth factor (PLGF) in plasma and placenta were measured on G20. Results Compared with the group C, the SBP and urinary protein levels were increased in the PE group, the PE+U₁ group and the PE+U₂ group. UTI decreased the SBP and urinary protein levels in PE rats, and the urinary protein level was lower in the PE+U₂ group (P<0.05). Compared with the group C, TNF-α and IL-6 levels were increased in the PE group and the PE+U₁ group, and only placental TNF-α level was increased in the PE+U₂ group (P<0.05). UTI reduced TNF-α and IL-6 levels in PE rats. The plasma and placental levels of TNF-α, IL-6 and the placental IL-6 level were lower in the PE+U₂ group (P<0.05). Compared with the group C, the PLGF levels were reduced, the vWF levels were increased in the PE group and the PE+U₁ group, but the vWF levels were only increased in the PE+U₂ group (P<0.05). UTI increased PLGF levels and reduced vWF levels in PE rats, and the levels of vWF were lower in the PE+U₂ group (P<0.05). Conclusion UTI can effectively inhibit inflammatory response in plasma and placenta of PE rats, reduce vascular endothelial injury, and alleviate hypertension and proteinuria of PE rats. The therapeutic effect of 10 000 IU·kg^-1·d^-1 UTI is better than 5 000 IU·kg^-1·d^-1.

Key words: pre-eclampsia, hypertension,pregnancy-induced, proteinuria, inflammatory response, ulinastatin

中图分类号:

R714.252

图/表 5

参考文献 19

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组别		n	G12		G13
C组		14	112.86±5.87		110.14±6.06
PE组		12	111.75±5.97		133.53±6.61^a
PE+U₁组		13	110.15±7.14		123.92±7.19^ab
PE+U₂组		13	113.39±5.32		118.23±8.88^ab
F			0.716		23.670^＊＊
组别	G15			G17		G19
C组	110.79±5.83			111.29±4.84		116.50±6.50
PE组	147.00±5.78^a			142.58±6.67^a		144.67±4.36^a
PE+U₁组	128.23±8.06^ab			126.69±7.78^ab		129.92±7.15^ab
PE+U₂组	122.02±6.04^ab			120.00±7.70^ab		123.31±5.62^abc
F	69.610^＊＊			47.980^＊＊		50.460^＊＊

组别		n	G12		G13
C组		14	112.86±5.87		110.14±6.06
PE组		12	111.75±5.97		133.53±6.61^a
PE+U₁组		13	110.15±7.14		123.92±7.19^ab
PE+U₂组		13	113.39±5.32		118.23±8.88^ab
F			0.716		23.670^＊＊
组别	G15			G17		G19
C组	110.79±5.83			111.29±4.84		116.50±6.50
PE组	147.00±5.78^a			142.58±6.67^a		144.67±4.36^a
PE+U₁组	128.23±8.06^ab			126.69±7.78^ab		129.92±7.15^ab
PE+U₂组	122.02±6.04^ab			120.00±7.70^ab		123.31±5.62^abc
F	69.610^＊＊			47.980^＊＊		50.460^＊＊

组别	n	G12	G19
C组	14	91.07±12.60	89.71±11.65
PE组	12	84.25±9.95	140.42±14.36^a
PE+U₁组	13	91.23±10.37	128.08±8.56^ab
PE+U₂组	13	84.46±10.34	100.85±11.16^abc
F		1.673	51.350^＊＊

组别	n	G12	G19
C组	14	91.07±12.60	89.71±11.65
PE组	12	84.25±9.95	140.42±14.36^a
PE+U₁组	13	91.23±10.37	128.08±8.56^ab
PE+U₂组	13	84.46±10.34	100.85±11.16^abc
F		1.673	51.350^＊＊

组别		血浆			胎盘
组别	n	TNF-α（ng/L）	IL-6（ng/L）	n	TNF-α	IL-6
C组	7	21.64±6.43	16.80±4.94	14	0.31±0.14	0.40±0.09
PE组	6	69.94±12.92^a	41.37±7.83^a	12	1.06±0.09^a	0.97±0.21^a
PE+U₁组	7	49.55±10.59^ab	27.01±4.62^ab	13	0.87±0.11^ab	0.68±0.18^ab
PE+U₂组	7	34.05±6.02^bc	19.97±2.97^b	13	0.71±0.12^abc	0.51±0.11^bc
F		32.660^＊＊	25.790^＊＊		95.860^＊＊	34.580^＊＊

乌司他丁缓解子痫前期大鼠高血压、蛋白尿和炎症反应的实验研究

Effects of UTI on alleviating hypertension, proteinuria and inflammatory response in PE rats

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组别		血浆			胎盘
组别	n	vWF（μg/L）	PLGF（ng/L）	n	vWF	PLGF
C组	7	0.66±0.29	184.54±38.00	14	0.24±0.07	0.56±0.10
PE组	6	1.81±0.57^a	94.48±34.75^a	12	0.61±0.10^a	0.24±0.13^a
PE+U₁组	7	1.19±0.18^ab	144.99±11.43^ab	13	0.47±0.11^ab	0.39±0.07^ab
PE+U₂组	7	0.98±0.10^abc	160.96±13.28^b	13	0.36±0.09^abc	0.48±0.07^b
F		13.440^＊＊	12.660^＊＊		36.660^＊＊	26.420^＊＊

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