Wang Tao, Leng Yu-fang, Zhang Yue, Kang Yu-qing, Xue Xing, Zhang Yan
Department of Anesthesiology, First Hospital of Lanzhou University, Lanzhou 730000, China.
Zhonghua Yi Xue Za Zhi. 2011 Apr 26;91(16):1130-5.
To investigate the protective effects of ischemic postconditioning and penehyclidine hydrochloride on gastric injury induced by ischemia-reperfusion of lower limb in rats.
The model of limb ischemia reperfusion injury was used to perform this experiment. One hundred and forty four male Wistar rats weighing 220 - 250 g were randomly divided into 4 groups: group I Control (C), group II Ischemic Reperfusion (IR), group III Ischemic postconditioning (IPO) and group IV penehyclidine hydrochloride (IPHC); C, IR, IPO and IPHC groups has been followed for 0(T(0)), 1(T(1)), 3(T(3)), 6(T(6)), 12(T(12)), or 24(T(24)) perfusion, all the groups were secondary separated into six subgroups as time point and each subgroup contained six rats, respectively. Blood samples from the inferior vena cava were taken for determination of LDH, CK activities and TNF-α, IL-10 content at every time point of reperfusion;the animals were killed at every time point respectively and the gastric were removed for determination of SOD, MPO, XOD and LDH activities, MDA content, and histological examination and the expression of HIF-1α was analyzed.
Compared with group C, IR, IPO and IPHC, in serum LDH and CK activities were increased, TNF-α and IL-10 content were increased (P < 0.05 or P < 0.01); and in gastric tissue MPO, XOD and LDH activities were increased and MDA content increased, while SOD activity decreased in group IR, IPO and IPHC (P < 0.05 or P < 0.01); and gastric tissue resulted in significant injury as evidenced by infiltrated of few neutrophils or eosinophils and rare neutrophils between the gastric mucosa or muscularis mucosa and the glands, interstitial vascular dilation hyperemia and small quantity hemorrhage from deep layers of mucosa or interstitial vascular dilation hyperemia, and the expression of HIF-1α was significantly increased (P < 0.01). Compared with group IR, IPO and IPHC in serum LDH and CK activities, TNF-α content decreased while IL-10 content were increased (P < 0.01); and in gastric tissue MDA content, MPO, XOD and LDH activities were decreased, and SOD activity increased in group IPO and IPHC (P < 0.05 or P < 0.01); and the histological injury were milder and the expression of HIF-1α was significantly decreased (P < 0.01). Compared with group IPO, IPHC, in serum LDH activities were makable decreased, CK activities were first increased and then declined, TNF-α content makable declined while IL-10 content were increased (P < 0.05 or P < 0.01), and the histological injury were milder and the expression of HIF-1α was makable decreased (P < 0.01) and in gastric tissue SOD activity were makable increased, MPO activities significantly decreased, MDA content increased at T(3), XOD activities increased after T(12), LDH activities increased at T(3) and declined after T(12) in group IPHC (P < 0.05 or P < 0.01).
The combination of ischemia postconditioning and postconditioning with penehyclidine hydrochloride can protect the gastric from ischemia-reperfusion injury induced by ischemia reperfusion of the lower limbs in rats, the main mechanism may be reducing post-ischemic oxidative damage, inflammatory reaction, amelio-rating microcirculatory and cellular energy metabolism et al. Additionally, this study found that the protective effects of penehyclidine hydrochloride on gastric injury induced by ischemia reperfusion of the lower limbs, were better than ischemic postconditioning, and the mechanism might be related to its anti-inflammatory effect, antioxidant action and prevention of cell injury et al.
探讨缺血后处理及盐酸戊乙奎醚对大鼠下肢缺血再灌注所致胃损伤的保护作用。
采用肢体缺血再灌注损伤模型进行本实验。将144只体重220 - 250 g的雄性Wistar大鼠随机分为4组：Ⅰ组为对照组（C），Ⅱ组为缺血再灌注组（IR），Ⅲ组为缺血后处理组（IPO），Ⅳ组为盐酸戊乙奎醚组（IPHC）；C、IR、IPO和IPHC组分别于再灌注0（T(0)）、1（T(1)）、3（T(3)）、6（T(6)）、12（T(12)）或24（T(24)）时相进行观察，每组再按时间点分为6个亚组，每个亚组各6只大鼠。于再灌注各时间点经下腔静脉取血测定乳酸脱氢酶（LDH）、肌酸激酶（CK）活性及肿瘤坏死因子-α（TNF-α）、白细胞介素-10（IL-10）含量；各时间点分别处死动物，取胃测定超氧化物歧化酶（SOD）、髓过氧化物酶（MPO）、黄嘌呤氧化酶（XOD）和LDH活性、丙二醛（MDA）含量，并进行组织学检查及分析缺氧诱导因子-1α（HIF-1α）的表达。
与C组比较，IR、IPO和IPHC组血清LDH、CK活性升高，TNF-α、IL-10含量增加（P < 0.05或P < 0.01）；胃组织MPO、XOD和LDH活性升高，MDA含量增加，SOD活性降低（P < 0.05或P < 0.01）；胃组织出现明显损伤，表现为胃黏膜或黏膜肌层与腺体之间有少量中性粒细胞或嗜酸性粒细胞浸润，黏膜深层或间质血管扩张充血、少量出血，HIF-1α表达明显增加（P < 0.01）。与IR组比较，IPO和IPHC组血清LDH、CK活性及TNF-α含量降低，IL-10含量增加（P < 0.01）；胃组织MDA含量、MPO、XOD和LDH活性降低，SOD活性升高（P < 0.05或P < 0.01）；组织学损伤较轻，HIF-1α表达明显降低（P < 0.01）。与IPO组比较，IPHC组血清LDH活性明显降低，CK活性先升高后下降，TNF-α含量明显下降，IL-10含量增加（P < 0.05或P < 0.01），组织学损伤较轻，HIF-1α表达明显降低（P < 0.01）；胃组织SOD活性明显升高，MPO活性明显降低，IPHC组T(3)时MDA含量增加，T(12)后XOD活性升高，T(3)时LDH活性升高，T(12)后下降（P < 0.05或P < 0.01）。
缺血后处理联合盐酸戊乙奎醚可保护大鼠下肢缺血再灌注所致的胃损伤，其主要机制可能是减轻缺血后氧化损伤、炎症反应，改善微循环及细胞能量代谢等。此外，本研究发现盐酸戊乙奎醚对大鼠下肢缺血再灌注所致胃损伤的保护作用优于缺血后处理，其机制可能与其抗炎、抗氧化及预防细胞损伤等作用有关。
