Mechanisms Of Myocardial Fibrosis Induced By Radiotherapy Combined With Recombinant Human Endostatin In Rats

Objective: The purpose of the study is to bring insights into the basic mechanisms of RIHD(Radiation-induced heart disease)that may lead to the identification of targets for intervention in the radiotherapy side effect.Methods: Sprague-Dawley rats were grouped as follows: RT(Radiotherapy,RT)25Gy”,”r E(recombinant human endostatin,r E)6mg/kg”,”r E 12mg/kg”,”RT 25Gy+r E 6mg/kg”,”RT 25Gy+r E 12mg/kg” and “blank control”groups.Use hematoxylin and eosin staining(HE),Masson trichrome staining,Western blotting(TGF-?1,Smad2/3,Collagen-I)and real-time PCR(TGF-?1,Smad2,Smad3,Collagen-I)were observed after 1,3 or 6 months.Results: Compared with the control group,there is no significant difference were found on groups RT 25 Gy and groups RT 25Gy+r E(6mg/kg,12mg/kg)after 1 months.Histopathologically,pronounced inflammation in ventricles was found in groups RT 25 Gy and groups RT 25Gy+ r E(6mg/kg,12mg/kg).Statistical differences of the TGF-?1 and Smad2 q PCR expression increased were found between the RT 25 Gy groups and controls after 3 month.In the RT 25 Gy groups and RT 25Gy+ r E(6mg/kg,12mg/kg)groups,consistent fibrosis were visible and Western blot and q PCR of TGF-?1 and Smad2 expression were increasing after a follow-up of 6 months.Compared with the control group,there is no significant difference were found on r E(6mg/kg,12mg/kg)groups after 1,3 and 6 months.Conclusion: Onset of cardiac fibrosis 3 month after rats were exposed to local heart irradiation with dose of 25 Gy and the progress would continues 6 month.Effect of recombinant human endostatin are mostely confined to angiogenic processes,when vessels are injuryed by irradiation,promoting fibrosis of RIHD,but effect of endostatin are diminished in the mature microvasculature.TGF-?1 and Smad2 signaling pathway are the signaling pathway of cardiac fibrosis induced by radiation.