Chen Xiao-Ming, Tang Bi-E, Sun Wei-Ming, Wang Yang
Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2014 Jan;30(1):70-3.
To investigate whether the cardioprotective effect of hemin against ischemia/reperfusion (I/R) injury is through the inhibition of calpain activity, and to explore its underlying mechanism.
Sixty-four SD rats were randomly divided into eight groups (n = 8): sham, I/R, MDL+ I/R, MDL, hemin + I/R, hemin, and ZnPP + hemin+ I/R, ZnPP. Iangendorff isolated rat heart perfusion model was used. The rat hearts were suffered from 40 min of ischemia followed by 30 min of reperfusion. After that, left ventricular developed pressure (LVDP) was recorded. Infarct size and release of lactate dehydrogenase (LDH) were measured. Calpain, heme oxygenase (HO), and caspase 3 activities were evaluated. Expression of calpastatin protein was detected by Western blot.
(1) After suffered from ischemia/reperfusion, the calpain activity and caspase 3 activity increased. MDL28170, an inhibitor of calpain, prevented ischemia/reperfusion induced increases in LDH and infarct size, improved the LVDP recovery. (2) Compared with ischema/reperfusion rat hearts, pretreatment of hemin enhanced the HO-1 activity, decreased the calpain and caspase 3 activities, declined LDH release and infarct size, and improved LVDP recovery. (3) Ischemia/reperfusion reduced the expression of calpastatin protein in rat hearts, which was inhibited by hemin pretreatment. And HO-1 inhibitor could abolish the cardioprotection of hemin.
Cardioprotective effect of hemin against ischemia/reperfusion injury is through the inhibition of calpain activity, the mechanism might be involved in the increase in calpastatin protein expression.
研究氯化血红素对缺血/再灌注（I/R）损伤的心脏保护作用是否通过抑制钙蛋白酶活性来实现，并探讨其潜在机制。
将64只SD大鼠随机分为8组（n = 8）：假手术组、I/R组、MDL + I/R组、MDL组、氯化血红素 + I/R组、氯化血红素组、锌原卟啉 + 氯化血红素 + I/R组、锌原卟啉组。采用Langendorff离体大鼠心脏灌注模型。大鼠心脏经历40分钟缺血后再灌注30分钟。之后，记录左心室舒张末压（LVDP）。测量梗死面积和乳酸脱氢酶（LDH）释放量。评估钙蛋白酶、血红素加氧酶（HO）和半胱天冬酶3的活性。通过蛋白质印迹法检测钙蛋白酶抑制蛋白的表达。
（1）缺血/再灌注后，钙蛋白酶活性和半胱天冬酶3活性增加。钙蛋白酶抑制剂MDL28170可防止缺血/再灌注诱导的LDH增加和梗死面积扩大，改善LVDP恢复。（2）与缺血/再灌注大鼠心脏相比，氯化血红素预处理可增强HO-1活性，降低钙蛋白酶和半胱天冬酶3活性，减少LDH释放和梗死面积，改善LVDP恢复。（3）缺血/再灌注降低了大鼠心脏中钙蛋白酶抑制蛋白的表达，氯化血红素预处理可抑制这一现象。HO-1抑制剂可消除氯化血红素的心脏保护作用。
氯化血红素对缺血/再灌注损伤的心脏保护作用是通过抑制钙蛋白酶活性实现的，其机制可能与钙蛋白酶抑制蛋白表达增加有关。
