Xia Zhong-Yuan, Gao Jin, Ancharaz Ameer Kumar
Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan 430060, China.
Chin J Traumatol. 2009 Jun;12(3):162-6.
To investigate the effect of ischemic postconditioning (IPO) on acute lung ischemia-reperfusion (I/R) injury and the protein expression of haeme oxygenase-1 (HO-1), a cytoprotective defense against oxidative injury.
After being anesthetized with chloralhy- drate, forty-eight healthy SD rats were randomly divided into 6 groups (8 in each): sham operation group (S group); I/R group: left lung hilum was clamped for 40 minutes followed by 105 minutes of reperfusion; IPO group: left lung hilum was clamped for 40 minutes and postconditioned by 3 cycles of 30 seconds of reperfusion and 30 seconds of reocclusion; Hemin (HM)+ I/R group: hemin, an inducer of HO-1 was injected intraperitoneally at 40 micromol/kg/day for two consecutive days prior to 40 minutes clamping of left lung hilum; ZnPPIX+IPO group: zinc protoporphyrin IX, an inhibitor of HO-1 was injected intraperitoneally at 20 mg/kg 24 hours prior to 40 minutes clamping of left lung hilum; and HM+S group: HM was administered as in the HM+I/R group without inducing lung I/R. Arterial partial pressure of oxygen (PaO(2)) and malondialdehyde (MDA) content in serum were assessed. The left lung was removed for determination of wet/dry lung weight ratio and expression of HO-1 protein by immuno-histochemical technique and for light microscopic examination.
The PaO(2) was significantly lower in all the experimental groups compared with sham group (90 mm Hg +/- 1 mm Hg). However, the values of PaO(2) in IPO (81 mm Hg +/- mm Hg) and HM+I/R (80 mm Hg+/- mm Hg) were higher than that in I/R (63 mm Hg +/- 9 mm Hg) and ZnPPIX+IPO (65 mm Hg +/- 8 mm Hg) groups (P less than 0.01). The protein expression of HO-1 in lung tissue was significantly increased in I/R group compared with S group (P less than 0.01). While the HO-1 protein expression was higher in IPO and HM+I/R groups as compared with I/R group (P less than 0.05, P less than 0.01). The lung wet/dry (W/D) weight ratio and MDA content in serum were significantly increased in I/R group as compared with S or HM+S groups (P less than 0.01), accompanied by severe lung tissue histological damage, which was attenuated either by IPO or by HM pretreatment (P less than 0.01, IPO or HM+I/R vs. I/R). The protective effect of IPO was abolished by ZnPPIX.
Ischemic postconditioning can attenuate the lung ischemia-reperfusion injury through upregulating the protein expression of HO-1 that leads to reduced post-ischemic oxidative damage.
探讨缺血后处理（IPO）对急性肺缺血-再灌注（I/R）损伤的影响以及血红素加氧酶-1（HO-1）的蛋白表达，HO-1是一种针对氧化损伤的细胞保护防御机制。
用氯水合醛麻醉后，将48只健康SD大鼠随机分为6组（每组8只）：假手术组（S组）；I/R组：左肺门夹闭40分钟，随后再灌注105分钟；IPO组：左肺门夹闭40分钟，然后进行3个循环的再灌注30秒和再夹闭30秒的后处理；血红素（HM）+I/R组：在左肺门夹闭40分钟前连续两天腹腔注射HO-1诱导剂血红素，剂量为40微摩尔/千克/天；锌原卟啉IX（ZnPPIX）+IPO组：在左肺门夹闭40分钟前24小时腹腔注射HO-1抑制剂锌原卟啉IX，剂量为20毫克/千克；HM+S组：按HM+I/R组的方法给予HM，但不诱导肺I/R。评估动脉血氧分压（PaO₂）和血清丙二醛（MDA）含量。取出左肺，通过免疫组织化学技术测定肺湿/干重比和HO-1蛋白表达，并进行光镜检查。
与假手术组（90毫米汞柱±1毫米汞柱）相比，所有实验组的PaO₂均显著降低。然而，IPO组（81毫米汞柱±毫米汞柱）和HM+I/R组（80毫米汞柱±毫米汞柱）的PaO₂值高于I/R组（63毫米汞柱±9毫米汞柱）和ZnPPIX+IPO组（65毫米汞柱±8毫米汞柱）（P<0.01）。与S组相比，I/R组肺组织中HO-1的蛋白表达显著增加（P<0.01）。与I/R组相比，IPO组和HM+I/R组的HO-1蛋白表达更高（P<0.05，P<0.01）。与S组或HM+S组相比，I/R组的肺湿/干（W/D）重比和血清MDA含量显著增加（P<0.01），伴有严重的肺组织组织学损伤，IPO或HM预处理均可减轻这种损伤（P<0.01，IPO或HM+I/R组与I/R组相比）。ZnPPIX消除了IPO的保护作用。
缺血后处理可通过上调HO-1的蛋白表达减轻肺缺血-再灌注损伤，从而减少缺血后的氧化损伤。
