Experiment Research Of RLj-RGD3 On Anti-thrombosis In Rats Induced By Carrageenan

ObjectiveTo investigate the effects of rLj-RGD3 on anti-thrombosis in rats induced by carrageenanMethodsTT, PT, APTT, hemorrheology, platelet aggregation and the level of TXB2 and PGI2 were determined to examine effect of rLj-RGD3 on nti-thrombosis in rats induced by carrageenan. The above blood parameters were measured after ip administration of rLj-RGD3at low (25), middle (50) and high (μg·kg- 1) doses to rats induced by carrageenan and after iv administration of rLj-RGD3 at low (12.5), middle (25,50) and high (100μg·kg- 1) doses to rats in compatison with positive,heparin, LAS and pentoxifylline.Results1.Effect of rLj-RGD3 on anti-thrombosis in mouse tail thrombosis induced by carrageenanIn comparison with NS+C group, the suppression percentage of rLj-RGD3 25,50,75μg·kg- 1 were 32.50% (p < 0.05), 44.63% (p < 0.01) and 64.94% (p < 0.01), thrombosis ratio for 10/10, 6/10, 4/10 respectively. suppression percentage of Heparin 400 IU·kg - 1 and LAS 18 mg·kg^-1 were 38.06 %, 40.31% and thrombosis ratio for 9/10, 8/10, respectively.2. Effect of rLj-RGD3 on coagulation time parameterThe results showed that rLj-RGD3 could not prolong dose-dependently TT,PT and APTT coagulation time in normal rats. rLj-RGD3 could prolong dose-dependently PT with corresponding percent lengthening of coagulation time being 17.80%( p<0.05),28.28% (p<0.01),47.81(p<0.01) in rats induced by carrageen.3. Effect of rLj-RGD3 on hemorrheologyrLj-RGD3 had no influence on whole blood viscosity and plasma viscosity in normal rats. low dose of rLj-RGD3 had no influence on high shear value and low shear value of whole blood viscosity and plasma viscosity in model rats induced by carrageenan.4. Effect of rLj-RGD3 on platelet aggregationrLj - RGD3 had influence on platelet aggregation induced by ADP and collagen and adrenaline .rLj - RGD3 could effectively inhibit platelet aggretion, the suppression percentage of rLj-RGD3(25, 50, 75μg·kg- 1) were 26.01%, 31.23%, 43.22% and 21.68%, (p > 0.05), 18.39% 19.90%, 31.57% (rLj-RGD3 and high dose group), LAS significantly positive control 31.08%; the suppression percentage of rLj - RGD3(12.5, 25.0,50.0,100.0μg·kg- 1) were 25.0 %,41.3 %,55.9 %and65.8 %, platelet aggregation induced by ADP. low dose group had no effect on platelet aggregation induced by collagen, others had significantly dose-respondent, 12.35%,16.40%,34.68%, with adrenaline-induced platelet aggregation, rLj-RGD3 low dose group had no effect, other dose groups of significant inhibiting platelet aggregation, inhibition percentage were 9.86%, 25.07%, 47.87% ,respectively, LAS had 39.61% and 21.05% ;rLj-RGD3 end concentration for 90.91, 62.50, 117.65μg·ml^-1 in vitro rats platelet aggregation induced by ADP in vitro respectively, inhibition percentage were 18.00%,25.32%, 52.23%. rLj - RGD3 end concentration for 14.49, 28.57, 42.25μg·ml^-1 platelet aggregation in vitro rats induced by collagen, inhibition percentage (p < 0.01) were 19.20%, 41.70%, 55.64%, respectively. rLj - RGD3 end concentration for 27.78, 54.05, 78.95μg·ml^-1 had inhibited platelet aggregation , inhibition percentage were 6.83%, 15.59%, 26.53% in vitro rats platelet aggregation induced by adrenaline in vitro rats, inhibition percentage of LAS inhibit positive control were 78.49%, 30.53% respectively. Above platelet aggregation experiment, the positive control of LAS didn't have influence on platelet aggregation adrenaline-induced. 5. Effect of of rLj - RGD3 on plasma values of TXA2 and 6-keto-PGF1αrLj - RGD3 can effectively reduce the rats TXA2 and PGI2 level and plasma ratio of content.rLj-RGD3 25,50,75μg·kg^-1 , TXB₂/6-keto-PGF1αwere 1.23±0.07,0.76±0.02,0.48±0.03(p<0.01),Heparin400IU·kg^-1,TXB₂ /6-keto-PGF1α(p<0.01)were 0.58±0.06 in model rats;rLj-RGD3 12.5μg·kg^-1,25μg·kg^-1,50μg·kg^-1and100μg·kg^-1(p<0.01),TXB₂/6-keto-PGF1αwere 0.78±0.03,0.61±0.02,0.48±0.03,0.27±0.01(p<0.01);Heparin200IU·kg^-1, TXB₂ /6-keto-PGF1α(p<0.01)were 0.31±0.02 in normal rats.ConclusionrLj-RGD3 has significant effects on anti-thrombosis, improving hemorrheology in rats induced by carrageen. rLj-RGD3 has significant effects on inhibiting platelet aggregation and can effectively reduce the rats TXA2 and PGI2 level and plasma ratio of content.