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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.
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Objective To examine the pathological changes in the myocardial tissues such as inflammatory response and fibrosis in a rat model of acute radiation-induced heart damage (RIHD),and to explore whether NF-κB and its downstream pathway are associated with acute radiation-induced myocardial fibrosis.Methods Fourteen nale adult Sprague-Dawley rats were randomly divided into control group and radiation group.Local heart irradiation was delivered to the precordial region of rats to establish an RIHD model in a single fraction with a dose of 20 Gy generated by a 6 MV linear accelerator.At 14 days after irradiation,the histopathological changes in myocardial and interstitial tissues were examined by HE staining;the distribution of collagen fibers was observed by Masson staining,and collagen volume fraction (CVF) was used as a semi-quantitative evaluation for myocardial collagen deposition,which was defined as the percentage of collagen area occupied in total area,and was compared using the independent-samples t test.The protein and mRNA expression levels of the NF-κB members p50 and p65 and the downstream pathway members hypoxia-inducible factor 1α(HIF-1o),connective tissue growth factor (CTGF),and type I (COL-1) were quantitatively analyzed by Western blot and qPCR,respectively.Results At 14 days after local heart irradiation,the radiation group showed significant myocardial edema and derangement,rupturc of some myocardial ceils,mild nuclear pyknosis,darkened nuclear staining,a small number of irregular nuclei,and myocardial interstitial inflammatory cell infiltration accompanied by increased fibroblast,as compared with the control group.The Masson staining showed that the collagen fibers in radiation group were widely distributed at the interstitial tissue and increased significantly compared with those in the control group;normal myocardial cells were in disordered array and had a tendency to be replaced by collagen fibers.The semi-quantitative analysis showed that radiation induced a significant increase in CVF (22.05％ vs.3.76％,P =0.003).Western blot and qPCR revealed that the protein and mRNA expression of p50,p65,HIF-1 α,CTGF,and COL-1 was significantly higher in the radiation group than in the control group (all P ＜ 0.05).Conclusions The pathological features of acute RIHD include significant myocardial edema and myocardial interstitial inflammatory cell infiltration accompanied by increased fibroblasts and collagen fibers.Radiation exposure can activate NF-κB and cause the upregulation of HIF-1α and CTGF at both protein and mRNA levels,which may play an important role in the progression of radiation-induced myocardial inflammation to fibrosis.
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Objective The purpose of this study is to study the clinical and pathological features of neurilemoma .Methods We observed the clinicopathologic features and immunohistochemical staining from eight patients with orbital neurilemoma between 2010.1~2012.12.Results Eight patients with classic neurilemoma were included in the study ,in which there were five males and three females ,aged between 21 and 63,mean age 35.The main symptom of the patients was exophthalmos ,including five cases of right eyes and three left eyes;2 cases of orbital floor and six above orbit ,lasting for one to ten years .The tumor diameter ranged between 1cm and 5 cm,an average of 3 cm,being pale and light yellow color .There were five cases of type Antoni A and one case of type was Antoni B among the six classic type neurilemoma .Two cases of ancient were neurilemoma ,in which one case was the histological structure of the classic type neurilemoma ,but there were more hypertrophy tumor cells , chromatin was coarse block atypia cells .The other one case with cells arranged disorderly ,which was mainly fine striated cells with scattered deeply stained atypia cells ,stromal transparent degeneration ,cystic degeneration .Im-munohistochemistry results showed that S -100(+),vimentin(+),ki67(-).Conclusion Antoni type B and ancient schwannoma are rare ,with complicated histologic characteristics .Combined with clinical features and im-munohistochemistry staining ,it can be diagnosed .
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Objective To observe the expression of proinflammatory factors messenger RNA (mRNA) in periretinal membrane of proliferative vitreoretinopathy. Methods Fourteen specimens of periretinal membrane were collected during vitrectomy, and they were made into paraffin sections.The presence of mRNA coding for IL-1,IL-6,IL-8 and TNF alpha was observed by in situ hybridization(ISH) with biotin labeled oligonuclotide probes respectively.The eyeball after corneal grafting was made as normal control. Results No expression of proinflammatory factors mRNA was found in normal human retina.Positive staining was present in 5 specimens.In these specimens, IL-1? mRNA was found in 3 specimens and TNF? mRNA was found in 3 specimens,there is 1 specimen expressed IL-8 mRNA and 3 specimens expressed IL-6 mRNA.In these positive specimens, one contained cells expressing mRNA for IL-1 ? beta and IL-6, and one exhibited cells expressing mRNA for IL-1??IL-8 and TNF ?,two membranes possessed positive cells for IL-6 and TNF? mRNA, one membrane contained IL-1? mRNA positive cells only. Conclusion These findings suggest that these cytokines may be locally produced by cells infiltrating epiretinal membranes. The expression of IL-1?, IL-6, IL-8 and TNF? mRNA within retinal membranes provides further evidence of a pathogenic role of these cytokines in proliferative vitreoretinopathy.