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低压与标准气压气腹对活体供肾切除术患者肾组织 syndecan-1 脱落及 VEGF 受体-2 表达的影响:一项随机对照研究。

Effects of low versus standard pressure pneumoperitoneum on renal syndecan-1 shedding and VEGF receptor-2 expression in living-donor nephrectomy: a randomized controlled study.

机构信息

Department of Anesthesiology and Intensive Care, Cipto Mangunkusumo Hospital, Universitas Indonesia, Jakarta, Indonesia.

Department of Anesthesiology, Cipto Mangunkusumo Hospital, Salemba Raya 6th, Jakarta, 10430, Indonesia.

出版信息

BMC Anesthesiol. 2020 Feb 4;20(1):37. doi: 10.1186/s12871-020-0956-7.

DOI:10.1186/s12871-020-0956-7
PMID:32019488
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7001365/
Abstract

BACKGROUND

Laparoscopic nephrectomy is a preferred technique for living kidney donation. However, positive-pressure pneumoperitoneum may have an unfavorable effect on the remaining kidney and other distant organs due to inflamed vascular endothelium and renal tubular cell injury in response to increased systemic inflammation. Early detection of vascular endothelial and renal tubular response is needed to prevent further kidney injury due to increased intraabdominal pressure induced by pneumoperitoneum. Transperitoneal laparoscopic living donor nephrectomy represented a human model of mild increasing intraabdominal pressure. This study aimed to assess the effect of increased intraabdominal pressure on vascular endothelium and renal tubular cells by comparing the effects of low and standard pressure pneumoperitoneum on vascular endothelial growth factor receptor-2 (VEGFR-2) expression and the shedding of syndecan-1 as the early markers to a systemic inflammation.

METHODS

We conducted a prospective randomized study on 44 patients undergoing laparoscopic donor nephrectomy. Subjects were assigned to standard (12 mmHg) or low pressure (8 mmHg) groups. Baseline, intraoperative, and postoperative plasma interleukin-6, syndecan-1, and sVEGFR-2 were quantified by ELISA. Syndecan-1 and VEGFR-2 expression were assessed immunohistochemically in renal cortex tissue. Renal tubule and peritubular capillary ultrastructures were examined using electron microscopy. Perioperative hemodynamic changes, end-tidal CO, serum creatinine, blood urea nitrogen, and urinary KIM-1 were recorded.

RESULTS

The low pressure group showed lower intra- and postoperative heart rate, intraoperative plasma IL-6, sVEGFR-2 levels and plasma syndecan-1 than standard pressure group. Proximal tubule syndecan-1 expression was higher in the low pressure group. Proximal-distal tubules and peritubular capillary endothelium VEGFR-2 expression were lower in low pressure group. The low pressure group showed renal tubule and peritubular capillary ultrastructure with intact cell membranes, clear cell boundaries, and intact brush borders, while standard pressure group showed swollen nuclei, tenuous cell membrane, distant boundaries, vacuolizations, and detached brush borders.

CONCLUSION

The low pressure pneumoperitoneum attenuated the inflammatory response and resulted in reduction of syndecan-1 shedding and VEGFR-2 expression as the renal tubular and vascular endothelial proinflammatory markers to injury due to a systemic inflammation in laparoscopic nephrectomy.

TRIAL REGISTRATION

ClinicalTrials.gov NCT:03219398, prospectively registered on July 17th, 2017.

摘要

背景

腹腔镜肾切除术是活体供肾的首选技术。然而,正压气腹可能会对残留肾脏和其他远处器官产生不利影响,这是由于炎症性血管内皮细胞和肾小管细胞损伤对全身炎症反应的增加。需要早期检测血管内皮细胞和肾小管细胞的反应,以防止由于气腹引起的腹内压增加进一步造成肾损伤。经腹腔腹腔镜活体供肾切除术代表了一种轻度增加腹内压的人类模型。本研究旨在通过比较低压力和标准压力气腹对血管内皮生长因子受体-2(VEGFR-2)表达和作为全身炎症早期标志物的 syndecan-1 脱落的影响,来评估腹内压增加对血管内皮细胞和肾小管细胞的影响。

方法

我们对 44 例接受腹腔镜供肾切除术的患者进行了前瞻性随机研究。受试者被分配到标准(12mmHg)或低压力(8mmHg)组。通过 ELISA 定量检测基础、术中、术后血浆白细胞介素-6、syndecan-1 和 sVEGFR-2。使用免疫组织化学评估肾皮质组织中 syndecan-1 和 VEGFR-2 的表达。使用电子显微镜检查肾小管和肾小管周围毛细血管的超微结构。记录围手术期血流动力学变化、呼气末二氧化碳、血清肌酐、血尿素氮和尿液 KIM-1。

结果

与标准压力组相比,低压力组术中及术后的心率、血浆白细胞介素-6、sVEGFR-2 水平及血浆 syndecan-1 水平均较低。低压力组近端小管 syndecan-1 表达较高。低压力组近端-远端小管和肾小管周围毛细血管内皮 VEGFR-2 表达较低。低压力组肾小管和肾小管周围毛细血管超微结构显示细胞膜完整、细胞边界清晰、刷状缘完整,而标准压力组显示细胞核肿胀、细胞膜脆弱、边界遥远、空泡化和刷状缘脱落。

结论

腹腔镜肾切除术中低压力气腹减轻了炎症反应,减少了 syndecan-1 的脱落和 VEGFR-2 的表达,作为肾小管和血管内皮的促炎标志物,减轻了全身炎症引起的损伤。

试验注册

ClinicalTrials.gov NCT:03219398,于 2017 年 7 月 17 日前瞻性注册。

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