Wang Hong-Gang, Li Zhi-Yong, Liu Xiao-Lin
Department of Orthopaedics and Microsurgery, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China.
Acta Pharmacol Sin. 2006 Aug;27(8):991-9. doi: 10.1111/j.1745-7254.2006.00357.x.
To investigate whether tanshinone IIA could improve the effect of UW solution for skeletal muscle preservation and to determine the dose range of tanshinone IIA providing optimal protection during ischemia and reperfusion.
Ischemic rat limbs were perfused with UW solution or UW plus tanshinone IIA (UW+T, 0.05, 0.1, or 0.2 mg/mL) for 0.5 h before reperfusion; controls (I/R) received no perfusion. Serum creatine phosphokinase (CPK), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) were measured pre-ischemia and after reperfusion (2-h, 4-h, and 6-h). Muscle water content, superoxide dismutase (SOD), malondialdehyde (MDA), adenosine triphosphatase (ATPase) were assessed pre-reperfusion and after 6-h reperfusion. Intercellular adhesion molecule-1 (ICAM-1) and apoptosis were detected after 6-h reperfusion. Reperfusion blood flow was monitored during reperfusion period.
UW and UW+T prevented luxury perfusion during reperfusion and inhibited ICAM-1 expression and apoptosis after 6-h reperfusion. Serum CPK, AST, and LDH levels in UW rats were significantly less than those in controls after 2-h reperfusion (no difference, 4-h or 6-h reperfusion). After 4-h ischemia, there were significant differences in water content, MDA, SOD, and ATPase between UW and controls, but no difference after 6-h reperfusion. All tests with UW+T rats were significantly different from control results at corresponding durations. Higher tanshinone doses improved results.
UW plus tanshinone IIA increased protection against I/R injury, suggesting that tanshinone IIA has clinical value.
研究丹参酮IIA是否能增强UW液对骨骼肌的保存效果,并确定丹参酮IIA在缺血再灌注期间提供最佳保护的剂量范围。
在再灌注前,用UW液或UW液加丹参酮IIA(UW+T,0.05、0.1或0.2mg/mL)灌注缺血大鼠肢体0.5小时;对照组(I/R)不进行灌注。在缺血前和再灌注后(2小时、4小时和6小时)测量血清肌酸磷酸激酶(CPK)、天冬氨酸转氨酶(AST)和乳酸脱氢酶(LDH)。在再灌注前和再灌注6小时后评估肌肉含水量、超氧化物歧化酶(SOD)、丙二醛(MDA)、三磷酸腺苷酶(ATPase)。在再灌注6小时后检测细胞间黏附分子-1(ICAM-1)和细胞凋亡情况。在再灌注期间监测再灌注血流量。
UW液和UW+T组在再灌注期间预防了过度灌注,并在再灌注6小时后抑制了ICAM-1表达和细胞凋亡。UW组大鼠在再灌注2小时后的血清CPK、AST和LDH水平显著低于对照组(在4小时或6小时再灌注时无差异)。缺血4小时后,UW组和对照组在含水量、MDA、SOD和ATPase方面存在显著差异,但在再灌注6小时后无差异。UW+T组大鼠在相应时间段的所有检测结果与对照组均有显著差异。较高剂量的丹参酮可改善结果。
UW液加丹参酮IIA增强了对缺血/再灌注损伤的保护作用,提示丹参酮IIA具有临床应用价值。