ABSTRACT
Objective:To explore the establishment of radiation-induced heart damage (RIDH) SD rat models caused by irradiation of 15Gy/3f and the changes in early detection indicators, and evaluate the effect of irradiation combined with recombinant human endostatin (Endostar).Methods:75 adult male SD rats were randomly divided into the blank control group (C group), Endostar group (E group), 25Gy irradiation group (MHD 25 group), 15Gy irradiation group (MHD 15 group) and 15Gy irradiation combined with Endostar group (MHD 15+ E group), respectively. Blood sample was taken to measure the CK, CK-MB, LDH and CRP at 24h, 48h and 15d after corresponding interventions. After cardiac echocardiography at 1, 3 and 6 months, 5 rats in each group were randomly sacrificed and myocardial tissues were collected for HE and Masson staining. Two-way ANOVA was employed for statistical analysis. Results:Compared with group C, myocardial fibrosis were observed in the MHD 15 group at 6 months ( P<0.05), which occurred later than that in the MHD 25 group. Ejection fraction (EF) and fractional shortening (FS) were significantly decreased after 3 months in each irradiation group (all P<0.05), whereas the degree of decrease was similar among all groups (all P>0.05). The expression levels of myocardial enzymes and inflammatory cytokines did not significantly differ among different groups (all P>0.05). Conclusions:In the early stage, exposure to 15Gy/3f irradiation can cause cardiac function damage in SD rat hearts, such as the reduction of EF and FS, and even lead to myocardial fibrosis in the late stage, which is delayed and less severe than high-dose irradiation. Irradiation combined with Endostar has no significant effect on radiation myocardial injury in rats.
ABSTRACT
At present,heart has become an important organ at risk during radiotherapy for thoracic,mediastinal and breast carcinoma.Heart is relatively sensitive to radiation because of its anatomical location and structure.The incidence of radiation-induced cardiac adverse events can affect the long-term survival of patients.In this article,the recent progress on the basic research of radiation-induced heart damage was described as follows.
ABSTRACT
At present, heart has become an important organ at risk during radiotherapy for thoracic, mediastinal and breast carcinoma. Heart is relatively sensitive to radiation because of its anatomical location and structure. The incidence of radiation-induced cardiac adverse events can affect the long-term survival of patients. In this article, the recent progress on the basic research of radiation-induced heart damage was described as follows.
ABSTRACT
Objective: To screen and optimize the modeling condition for radiation-induced heart damage (RIHD) models characterized by inflammatory-fibrosis pathological injury. Methods: The rats were irradiated with single whole-body X-ray to screen the maximal tolerated dose. Based on the screened whole-body dose, single local heart irradiation doses were used to screen the minimal X-ray dose which could induce the significant cardiac damage. And the RIHD rat model was established by exposure to the screened dose of X-ray. Tissue samples were harvested 1 day, 1 week, 2 weeks, 4 weeks and 6 weeks after irradiation. The cardiac pathological injury score, collagen volume fraction (CVF) in myocardial tissues by Masson staining, plasma myocardial enzyme level, and the expression of inflammatory and fibrosis factors in myocardial tissues were examined for evaluating the animal model. Results: The tolerance dose of whole-body irradiation was lower than 16 Gy for rats. Local irradiation dose at least 25 Gy could induce RIHD in rats. The pathological injury score of myocardial tissues, CVF in myocardial tissues and creatine kinase isoenzyme MB (CK-MB) and cardiac troponin (cTn) in plasma were increased in the RIHD model rats. Inflammatory factors including nuclear factor (NF)-κB p65, NF-κB p50 and tumor necrosis factor α (TNF-α) in myocardial tissues were increased 1 day after irradiation in the RIHD rats and maintained high to the fourth week. The expression levels of fibrotic molecules transforming growth factor β1 (TGF-β1), collagen type I (Col I) and Col III in myocardial tissues were increased gradually, and reached the peaks at week 4 after irradiation. Conclusion: Stable RIHD rat model can be established by irradiating the precardiac region with 25 Gy X-ray. Pathological observation and CVF can dynamically reflect the early inflammatory changes and the progression of fibrosis in RIHD rats. The sustained high expression of NF-κB p65, NF-κB p50 and TNF-α at early stage and the progressive increases of TGF-β1, Col I and Col III can be used to evaluate the acute inflammatory injury and delayed fibrosis in the RIHD inflammatory-fibrosis model.
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Objective To investigate whether pyrrolidine dithiocarbamate (PDTC) can attenuate the acute radiation-induced heart damage (RIHD) by inhibiting the activation of NF-κB and its downstream signaling pathways in rat models. Methods Twenty-one male adult Sprague-Dawley (SD) rats were randomly divided into the blank control, irradiation and PDTC plus irradiation groups (n=7 for each group). In the irradiation and PDTC+ irradiation groups,the rats received 6 MV X-ray at a single fraction of 20.0 Gy. In the PDTC+ irradiation group, intraperitonal injection of PDTC was administered at a dose of 120 mg/kg body weight,30 minutes prior to radiation, once daily for 1-14 days. On the 14thday,pathological changes of myocardial tissue were observed. Masson's trichrome staining was performed to calculate the collagen volume fraction (CVF) of myocardial cells. The expression levels of NF-κB family members including p50, p65,HIF-1α,connective tissue growth factor (CTGF) and collagen type 1(COL-1) proteins and mRNA were quantitatively measured by Western blot and quantitative real-time PCR (qPCR). Statistical analysis was conducted by using t-test. Results HE staining demonstrated that compared with the irradiation group, the severity of myocardial edema was alleviated,the infiltration of inflammatory cells was mitigated and the quantity of fibroblasts was reduced in the PDTC+irradiation group. Masson's trichrome staining revealed that PDCT intervention could decrease the deposition of collagen fiber in the interstitial tissues. Semi-quantitative analysis demonstrated that the CVF value in the PDTC+irradiation group was (9.99± 0.32)%, significantly lower compared with (22.05±0.21)% in the irradiation group (P<0.05). Western blot and qRT-PCR demonstrated that the expression levels of p50,p65,and HIF-1αproteins and mRNA in the PDTC+ irradiation group were significantly down-regulated compared with those in the irradiation group (all P<0.05). Compared with the irradiation group,the expression levels of CTGF protein and mRNA tended to decline (all P>0.05),and the expression levels of COL-1 protein and mRNA were equally inclined to decrease (P<0.05 and P>0.05). Conclusion PDTC can alleviate the acute RIHD by suppressing the activation of NF-κB and its downstream HIF-1α transcription.