治疗性高碳酸血症对大鼠肝缺血再灌注损伤后炎症和细胞凋亡的影响。

Effects of therapeutic hypercapnia on inflammation and apoptosis after hepatic ischemia-reperfusion injury in rats.

机构信息

Department of Anesthesiology, second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150086, China.

出版信息

Chin Med J (Engl). 2010 Aug;123(16):2254-8.

PMID:20819675

Abstract

BACKGROUND

Therapeutic hypercapnia (TH) has been demonstrated to protect several organs ischemia-reperfusion injury. The study aimed to investigate the effects of therapeutic hypercapnia on hepatic ischemia-reperfusion injury (HIRI).

METHODS

Thirty adult male Wistar rats weighing (250+/-20) g were randomized into 3 groups (n=10 in each), group C (control group), group A (hypercapnia group) and group B (CO2 preconditioning group). A segmental ischemia of the liver was induced by interrupting the blood vessels including the bile duct to the median and left lateral lobes for 60 minutes and all the animals were sacrificed after 240 minutes observation period of reperfusion. Mean arterial pressure (MAP) and the blood gases were measured before ischemia (baseline) and at 30, 60, 120, 180 and 240 minutes after reperfusion. Arterial blood samples were obtained for determination of serum levels of TNF-alpha, IL-10, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT). The histopathology of liver tissues was evaluated by light microscopy. The NF-kappaB expression and apoptotic hepatocytes were respectively determined by immunohistochemistry and TUNEL assay.

RESULTS

The serum levels of liver enzymes and TNF-alpha were significantly decreased while the IL-10 level was significantly increased in groups A and B than in group C (P<0.05), and group B surpassed group A (P<0.05). The histopathological scores, the NF-kappaB immunohistochemical score (IHS) and apoptotic index were significantly lower in groups A and B than in group C (P<0.05), and the decrease in group B was more obvious than in group A (P<0.05).

CONCLUSION

Therapeutic hypercapnia attenuates ischemia-reperfusion injury to the liver. Moreover, the effects of CO2 preconditioning are outstandingly notable.

摘要

背景

治疗性高碳酸血症（TH）已被证明可保护多种器官的缺血再灌注损伤。本研究旨在探讨治疗性高碳酸血症对肝缺血再灌注损伤（HIRI）的影响。

方法

30 只成年雄性 Wistar 大鼠（体重 250±20）g，随机分为 3 组（每组 10 只），C 组（对照组）、A 组（高碳酸血症组）和 B 组（CO2 预处理组）。通过阻断包括胆管在内的肝中、左外侧叶的血管，诱导肝节段性缺血 60 分钟，所有动物在再灌注观察期 240 分钟后处死。在缺血前（基线）和再灌注后 30、60、120、180 和 240 分钟测量平均动脉压（MAP）和血气。采集动脉血样，测定血清肿瘤坏死因子-α（TNF-α）、白细胞介素-10（IL-10）、血清天门冬氨酸氨基转移酶（AST）和丙氨酸氨基转移酶（ALT）水平。通过光镜评估肝组织病理学变化。通过免疫组化和 TUNEL 检测法分别测定 NF-κB 表达和凋亡的肝细胞。

结果

与 C 组相比，A 组和 B 组的血清肝酶和 TNF-α水平显著降低，IL-10 水平显著升高（P<0.05），且 B 组优于 A 组（P<0.05）。与 C 组相比，A 组和 B 组的组织病理学评分、NF-κB 免疫组化评分（IHS）和凋亡指数均显著降低（P<0.05），且 B 组降低更明显（P<0.05）。