Wang W, Xiao Q, Hu X-Y, Liu Z-Z, Zhang X-J, Xia Z-P, Ye Q-F, Niu Y
Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, China.
The Third Xiangya Hospital of Central South University, Research Center of National Health Ministry on Transplantation Medicine Engineering and Technology, Changsha, China.
Transplant Proc. 2018 Jan-Feb;50(1):259-266. doi: 10.1016/j.transproceed.2017.12.019.
Mild hypothermia is known to be protected against ischemia reperfusion (IR) injury. But the exact mechanisms of protection have not yet been fully understood and its usage has been limited. Mild hypothermia pretreatment (MHP) is used to investigate the mechanisms of the protective effects against liver IR injury.
Anesthetized male Sprague-Dawley rats were randomly divided into five groups including the normal group (N), sham group (S), MHP group, normothermia pretreatment (NP) + IR group, and the MHP + IR group. In the pretreatment groups, mild hypothermia (32.2 ± 0.3°C) and normothermia (37 ± 0.5°C) pretreatment were applied for 2 hours, respectively. Then the IR groups suffered partial (70%) hepatic ischemia for 1 hour and reperfusion for 6 hours. At last, hepatic injury, apoptosis, and protein expression were assessed.
Levels of serum alanine transaminase, hepatic injury, hepatocyte apoptosis, and c-Jun N-terminal kinase (JNK) phosphorylation were significantly higher in the IR groups. But when compared to NP, all these changes induced by IR were markedly attenuated by MHP. Serum alanine transaminase levels were 383.4 ± 13.1U/L in the MHP + IR group and 951.3 ± 39.4 U/L in the NP + IR group. The histologic score of liver injury in the MHP + IR group was 4.83 ± 1.17, whereas in the NP + IR group it was 10.5 ± 1.05. The proportion of apoptotic cells in the MHP + IR group was 11.58 ± 0.60, but in the NP + IR group, it was 44.95 ± 1.61. The phosphorylation of JNK was also significantly reduced in the MHP + IR group. All these differences are statistically significant (P < .05).
MHP could markedly reduce liver IR injury, and these protective effects may be mainly exerted via inhibition of JNK phosphorylation.
已知轻度低温可预防缺血再灌注（IR）损伤。但其确切的保护机制尚未完全明确，且其应用受到限制。轻度低温预处理（MHP）用于研究其对肝脏IR损伤保护作用的机制。
将麻醉后的雄性Sprague-Dawley大鼠随机分为五组，包括正常组（N）、假手术组（S）、MHP组、正常体温预处理（NP）+IR组和MHP+IR组。在预处理组中，分别进行轻度低温（32.2±0.3°C）和正常体温（37±0.5°C）预处理2小时。然后IR组经历部分（70%）肝脏缺血1小时并再灌注6小时。最后，评估肝脏损伤、细胞凋亡和蛋白表达。
IR组血清丙氨酸转氨酶水平、肝脏损伤、肝细胞凋亡和c-Jun氨基末端激酶（JNK）磷酸化水平显著更高。但与NP组相比，IR诱导的所有这些变化在MHP组中均明显减轻。MHP+IR组血清丙氨酸转氨酶水平为383.4±13.1U/L，NP+IR组为951.3±39.4U/L。MHP+IR组肝脏损伤的组织学评分为4.83±1.17，而NP+IR组为10.5±1.05。MHP+IR组凋亡细胞比例为11.58±0.60，但NP+IR组为44.95±1.61。MHP+IR组JNK的磷酸化也显著降低。所有这些差异均具有统计学意义（P<0.05）。
MHP可显著减轻肝脏IR损伤，这些保护作用可能主要通过抑制JNK磷酸化来发挥。
