Addition of tanshinone IIA to UW solution decreases skeletal muscle ischemia-reperfusion injury.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
UW plus tanshinone IIA increased protection against I/R injury, suggesting that tanshinone IIA has clinical value.
Wang
Hong-Gang
HG
Department of Orthopaedics and Microsurgery, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China.
Li
Zhi-Yong
ZY
Liu
Xiao-Lin
XL
D045784:Abietanes; D000241:Adenosine / Q000494:pharmacology; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001219:Aspartate Aminotransferases / Q000097:blood; D003402:Creatine Kinase / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000494:pharmacology; D006614:Hindlimb; D007328:Insulin / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018482:Muscle, Skeletal / Q000098:blood supply / Q000378:metabolism*; D019188:Organ Preservation Solutions / Q000494:pharmacology*; D010616:Phenanthrenes / Q000008:administration & dosage / Q000494:pharmacology*; D011887:Raffinose / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology; D013482:Superoxide Dismutase / Q000378:metabolism
D045784:Abietanes; D007328:Insulin; D019188:Organ Preservation Solutions; D010616:Phenanthrenes; C055206:University of Wisconsin-lactobionate solution; C021751:tanshinone; D018799:Intercellular Adhesion Molecule-1; D008315:Malondialdehyde; D000493:Allopurinol; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase; D001219:Aspartate Aminotransferases; D003402:Creatine Kinase; D000251:Adenosine Triphosphatases; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose