The Mechanism And Significance Of The Merged Body Irradiation Injury Trauma Local Fibroblasts Change

Signiflcances and mechanisms of wound fibroblastsabnormalities in rats after combined total bodyirradiation(TBI) injuryAbstractWound accompanied with local bleeding, infection, diabetes mellitus or radiation injury will impair healing, total body irradiation(TBI) injury results in wounds healing more slowly. Wound repair is a multistep process consisting of inflammatory cell infiltration, tissue regrowth, and remodeling, the second is the most critical and important. Fibroblasts in wound sites are thought to play a central role in the processes of wound repopulation because they are the major components of granulation tissues, fibroblasts also participate in remodeling process by synthesizing extracellular matrix, such as collagen, fibronectin and hyaluronic acid, and so on. The functions of fibroblasts are under the influence of cytokines, fibroblasts can secrete cytokines, too. Therefore, fibroblasts are the most important cell types during wound healing, its abnormalities will inevitably impair wound healing. Studies on the alterations of fibroblasts are of great importance for understanding the mechanisms of wound healing and improving wound healing. Previous reports have demonstrated that TBI injury results in wound healing more slowly, but the mechanisms are not fully elucidated. In the present study we examined the alterations of wound fibroblasts numbers and functions in rats combined with TBI injury to further understand the mechanisms of impaired wound healing. The results and conclusions are summarized as follows:1.Inflammatory response in wound sites was significantly attenuated inrats combined with TBI injury as comPared with simple incisional injurywhich is pwtia1ly caused by the inhibition of nuc1ear factor kaPpa B activation.2. The numbers reduction and dysfunction of fibroblasts in wound sitesin rats combined with TBI injury affected the processes of inflammatoryresponse, wound repopulation, re-epithelial and tissue remode1ing, which arethe major causes of impaired wound healing.3. The concentrations of PCNA in wound sites were significantlydecreased in rats combined with TBI injury as compared with simple incisionalinjury which is coincident with the a1terations of wound fibroblasts numbers,suggesting that the reduction of wound fibroblasts is due to the inhibition offibroblast proliferation. The concentrations of Cyclin E and CDK4 in woundsites were a1so decreased in rats combined with TBI injury, but the a1terationsof Cyc1in E and CDK4 were earlier than that of fibroblast, indicating that thereductions of Cyclin E and CDK4 lead to the reduction of fibroblast byinhibiting the transition of cel1 cycle from G1 phase to S phase.4. The apoptosis of fibroblasts in wound sites were significantlyincreased in rats combined with TBI injury as compared with simple incisionalinjury which was negative1y correlated to the alteration of fibroblasts numbers,suggesting that the increment of aPoptosis is one of the reason of the reductionof fibroblast numbers. Bcl-2 and Bax played a great role in the increment offibroblast aPoptosis in rats combined TBI injUry.5. The concenirations of P53 in wound sites were significantly increasedin rats combined with TBI injury, which wi1l not only inhibit fibroblastsproliferation, but a1so increase aPoptosis of fibroblasts, and ultimately leadingto the reduction of fibroblasts numbers.6. The concentrations of FGF-2, NGF, type I col1agen and fibronectinin wound sites were significantly decreased in rats combined with TBI injuryas compared with simple incisional injury which indicates that there existIIIdysfunctions of fibroblasts after combined TBI injury.7.Disorder of the networks between fibroblasts, cytokines and extracellular matrixs delayed the processes of wound healing after combined TBI injury.8.The facts that the biological behavioures of fibroblasts derived from wound sites altered after combined TBI injury and fibroblasts were less response to NGF s...