Inhibitive Effect Of Tanshinone â…¡_A In Intimal Proliferation In Iliac Artery Following Balloon Injury In Rabbit

Objective: 1, to assess the preventive effect of tanshinone II_A in intimal thickening and smooth muscle cells ( SMC) proliferation; 2, to assess the time-dependent effect of tanshinone II_A in intimal thickening and SMC proliferation; 3, initially assess restenosis-preventing mechanism of tanshinone II_A after PCI.Materials and Methods: Thirty male pure breed New Zealand white rabbits, with a mean weight of 2.5~3 kilogram, were cathetered trans left femoral artery, and underwent experimental balloon injury in left iliac artery. Then the rabbits were assigned into treatment group(n =15) and control group( n = 15), paired with weights. Tanshinone II_A sulfonic acid natrium was injected intravenously with 7.5 ~ 9 mg/day for 6 days in treatment group. Injection tanshinone II_A sulfonic acid natrium was diluted to 4ml. Saline of equivalence was venously injected for 6 days in contol group. The balloon injured arteries were harvested in the 7th, 14th, and 28th days after balloon injury, and cleared with saline constant low pressure (2 atm). Paraffin sections were made, and treated with HE staining, apoptosis TUNEL analysis, and collagen staining. Results: (1) HE staining analyse: Media and intimal areas in treatment groupat 14th day post-operation were larger than that in the 7th day (P=0.003 and < 0.001 respectively). Media and intimal areas in treatment group decreased at the 28th day post-operation, whilst increased in control. Both media and intimal areas were significantly different ( P < 0.001 respectively). (2) Tunel analysis discovered that, apoptosis reached peak in both treatment and control groups at the 28th post-operation. Differences of apoptosis cells counts in media and intimal between treatment and control groups were non-significant at the 7, and 28th days, whilst differences at the 14th day were significant (P=0.031 and 0.029 respectively). Apoptosis cells counting in treatment group at the 14th day increased more dramatically than in the control. (3) Analysis of Collagen fibers staining found that a weak positive staining was shown at the 7th day post-operation in both groups, whilst a strong positive result was seen at the 14th day in control group. Positive results were even shown at the 14th day in treatment group, but less strong than that of the control. At the 28th day post-operation, collagen fiber staining become weak in treatment group, but increased in the control. Difference between both group in the 28th day post-operation was significant (P=0.017). Time-dependence tendency of collagen fiber changing was statistically significant (P = 0.005).Conclusion: Intravenous tanshinone IIA can inhibite intimal proliferation after arterial balloon injury in vivo in rabbits. The effect becomes valid to prevent restenosis partly by decrease deposition of extracellular matrix such as collagen at the 14th day, and by the induction of apoptosis at the 28th day. Clinical effect of tanshinone IIA is still needed further evaluation.