Department of Electrocardiogram, Linyi People's Hospital, No. 49 Yizhou Road, Linyi, 276000, Shandong, People's Republic of China.
Department of Neurology, Linyi People's Hospital, No. 49 Yizhou Road, Linyi, 276000, Shandong, People's Republic of China.
Inflammation. 2017 Dec;40(6):1903-1911. doi: 10.1007/s10753-017-0631-4.
Schisandrin B (Sch B), an active composition isolated from the fruit of Schisandra chinensis, has been proved to possess antiinflammatory, antioxidant and anti-endoplasmic reticulum (ER) stress effects in many rodent tissues. However, the exact mechanism of cardioprotective effect of Sch B still needs more study. Here, we detected the effects of Sch B on myocardial ischemia/reperfusion (I/R) injury rats. I/R injury model in this study was established by left anterior descending coronary artery ligation for 40 min followed by 1 h of reperfusion. Male healthy rats were randomly divided into five groups: the sham, I/R, Sch B (20 mg/kg) + I/R, and Sch B (40 mg/kg) + I/R, Sch B (80 mg/kg) + I/R, with 10 rats in each group. We showed that Sch B treatment significantly protected against myocardial I/R injury, as demonstrated by the decrease in the percentage of infarct formation assessed by 2,3,5-triphenyl tetrazolium chloride (TTC) staining in representative heart tissue slices, comparing with the I/R control group. The levels of creatine kinase (CK), lactate dehydrogenase (LDH), malondialdehyde (MDA), and total superoxide dismutase (T-SOD) were tested. The ER stress-related proteins such as C/EBP homologous protein (CHOP), activating transcription factor 6 (ATF6), and (PKR)-like ER kinase (PERK) were further measured by western blot, and their messenger RNA levels were measured by real-time PCR. The apoptosis of heart tissue cells was also tested through the expressions of caspase-9, caspase-3, Bcl-2, and Bax proteins. Collectively, these results revealed that Sch B exerts protection role on myocardial I/R injury through decreasing oxidative reaction, suppressing ATF6 and PERK pathway, and attenuating ER stress-induced apoptosis.
五味子丙素（Sch B）是从五味子果实中分离得到的一种活性成分，已被证明具有抗炎、抗氧化和抗内质网（ER）应激作用，在许多啮齿动物组织中均有体现。然而，Sch B 的确切心脏保护作用机制仍需要进一步研究。在这里，我们检测了 Sch B 对心肌缺血/再灌注（I/R）损伤大鼠的影响。本研究中的 I/R 损伤模型通过左前降支冠状动脉结扎 40min 后再灌注 1h 建立。雄性健康大鼠随机分为五组：假手术组、I/R 组、Sch B（20mg/kg）+I/R 组、Sch B（40mg/kg）+I/R 组、Sch B（80mg/kg）+I/R 组，每组 10 只。我们发现，Sch B 治疗可显著减轻心肌 I/R 损伤，这可通过 TTC 染色评估代表性心脏组织切片中梗死形成百分比来证明，与 I/R 对照组相比，梗死形成百分比降低。还测试了肌酸激酶（CK）、乳酸脱氢酶（LDH）、丙二醛（MDA）和总超氧化物歧化酶（T-SOD）的水平。通过 Western blot 进一步测量 ER 应激相关蛋白，如 C/EBP 同源蛋白（CHOP）、激活转录因子 6（ATF6）和（PKR）样内质网激酶（PERK），并通过实时 PCR 测量其信使 RNA 水平。还通过 caspase-9、caspase-3、Bcl-2 和 Bax 蛋白的表达检测心脏组织细胞的凋亡。综上所述，这些结果表明，Sch B 通过减少氧化反应、抑制 ATF6 和 PERK 通路以及减轻 ER 应激诱导的细胞凋亡，对心肌 I/R 损伤发挥保护作用。
