丹参多酚酸对心肌缺血大鼠血清及心脏组织炎症因子的保护作用

Protective effects of Salvianolic acid on myocardial ischemic injury of rats from the aspect of inhibiting inflammatory reaction

目的研究丹参多酚酸对心肌缺血损伤大鼠心肌酶与炎症因子水平的影响。方法按照体重将SD雄性大鼠随机分为4组:假手术组、模型组和低高2个剂量(丹参多酚酸18,36 mg·kg-1)实验组,每组15只,腹腔注射给药。假手术组和模型组按同等剂量注射蒸馏水,给药第4天,结扎冠状动脉左前降支建立心肌缺血模型。术后6 h,眼内眦取血,以酶联免疫吸附法检测血清肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)和乳酸脱氢酶(LDH)水平;于24 h取心脏,苏木素-伊红(HE)染色,光学显微镜下观察心肌组织病理变化,酶联免疫吸附法检测血清血肌肌钙蛋白(c Tn T)、肿瘤坏死因子α(TNF-α)和心肌组织匀浆髓过氧化物酶(MPO)含量。结果心肌缺血6 h后,假手术组CK为(529.61±141.93)U·L^(-1),CK-MB为(708.12±385.93)U·L^(-1),LDH为(330.12±158.38)U·L^(-1);模型组CK为(996.42±413.42)U·L^(-1),CK-MB为(1346.11±558.30)U·L^(-1),LDH为(520.12±154.76)U·L^(-1);低高2个剂量实验组CK分别为(499.45±159.33),(514.91±98.82)U·L^(-1),CK-MB分别为(831.42±385.11),(592.10±206.32)U·L^(-1),LDH分别为(462.62±229.68),(437.72±175.80)U·L^(-1);与假手术组相比,模型组大鼠血清CK、CK-MB、LDH水平明显升高,差异有统计学意义(P<0.05);与模型组比较,低高2个剂量实验组能明显降低大鼠血清CK、CK-MB的含量,差异有统计学意义(均P<0.05)。心肌缺血24 h,假手术组和模型组c Tn T分别为(294.12±55.10),(513.00±69.71)pg·m L^(-1),差异有统计学意义(P<0.05);给药后,低高2个剂量实验组c Tn T分别为(431.12±106.00),(338.80±76.92)pg·m L^(-1),与模型组比较,高剂量实验组差异有统计学意义(P<0.05)。术后24 h,假手术组和模型组TNF-α分别为(118.90±17.58),(156.00±28.24)pg·m L^(-1),差异有统计学意义(P<0.05);给药后,低高2个剂量实验组TNF-α分别为(136.05±34.00),(125.06±30.13)pg·m L^(-1),与模型组比较,高剂量实验组差异有统计学意义(P<0.05)。假手术组和模型组MPO分别为(32.25±3.75),(104.83±22.87)U·L^(-1),差异有统计学意义(P<0.01);给药后,低高2个剂量实验组MPO分别为(91.70±21.57),(68.00±18.47)U·L^(-1),与模型组比较,高剂量实验组差异有统计学意义(P<0.01)。结论丹参多酚酸具有心肌保护作用,能明显减轻心肌细胞损伤,减少心肌组织炎性细胞浸润,这可能与降低TNF-α、MPO等炎性介质水平有关。

Objective To investigate the protective effects of Salvianolic acid on myocardial ischemic injury of rats from the aspect of inhibiting inflammatory reaction. Methods Sixty Sprague Dawley （SD） male rats were randomly divided into four groups （n= 15 per group） ： sham operation group, model group, experimental - high （36 mg · kg^-1 ） group, experimental - low （ 18 mg · kg^-1） group with intraperitoneal injection dosing. Same amount of distilled water was injected to sham operation group and model group, lasting for 4 days. Myocardial ischemia model was established by coronary artery ligation of left anterior descending （LAD） branch after the last administration. Six hours after the operation, the blood of eye canthus was collected to assay the levels of creatine kinase（ CK）, MB isoenzyme of creatine kinase （CK -MB） and lactate de- hydrogenase （LDH） in serum. The heart was collected 24 h after the operation, stained by hematoxylin eosin （HE） and checked the pathological change of the cardiac muscle tissue, assayed the cardiac troponin （ cTnT）, tumor necrosis factor α （TNF -α） in serum and myeloperoxidase （MPO） was measured in myocardial tissue homogenate. Results After 6 hours＇ myocardial ischemia, the serum CK in sham operation group was （529.61 ± 141.93 ） U · L^-1, CK-MB was （708.12±385.93） U · L^-1, LDH was （330. 12 ± 158.38） U · L^-1 and cTnT was （294. 12±55.10） pg. mL-lafter 24 hours＇ myocardial ischemia. The serum CK in model group was （996. 42 ＋413.42） U · L^-1, CK-MB was （1346. 11 ±558.30） U · L^-1, LDH was （520. 12±154.76） U · L-land cTnTwas （513.00 ±69.71） pg · mL^-1 after 24 hours＇ myocardial ischemia. The serum CK in experimental- low and experimental -high groups were （499.45 ±159.33）,（514.91±98.82）U · L^-1, CK-MB were （831.42 ±385.11）,（592.10 ±206.32） U.L^-1 LDHwere （462.62±229.68） （437.72±175.80）U. L^-1 and cTnTwere （431.12±106.00） （338. 80±76. 92）pg · mL^-1 after 24 hours＇ myocardial ischemia. Compared with the sham operation group, the CK, CK - MB and LDH value in the serum of model group increased significantly （ P 〈 0. 05 ）. Compared with the model group, the salvianolic acid significantly both can decrease the CK and CK - MB in serum （P 〈 0. 05 ）. Compared with sham operation group, the cTnT value in the serum of model group increased significantly （P 〈 0.05）. Compared with model group, high dosage of salvianolic acid could significantly decrease the cTnT value （ P 〈 0. 05 ）. After 24 hours＇ myocardial ischemia, the TNF - α in serum of sham operation group was （ 118.90 ±17.58 ） pg · mL^- 1, the MPO in heart tissue was （32. 25 ±3.75） U · L^-1. The TNF - α in serum of model group was （ 156. 00±28. 24） pg · mL^-1, the MPO in heart tissue was （104. 83±22. 87） U · L^-l. The TNF -α in serum of experimental -low and experimen- tal- high groups were （136.05 ± 34.00）, （125.06 ± 30. 13） pg ·mL^-1, the MPO in heart tissue were （91.70 ±21.57） , （68.00±18.47） U · L^-1. Compared with sham operation group, the TNF - ct values in the serum and the MPO value in model group increased significantly （ P 〈 0. 05 ）. Compared with model group, these values of experimental - high group decreased with significantly （ all P 〈 O. 05 ）. Conclusion Salvianolic acid showed the protection of myocardial tissue, which also could significantly reduce the myocardial cell injury and inflammatory cell infiltration of cardiac myoeytes, which could be related with the decreased levels of TNF - α and MPO.