Inthe present study, we evaluated thecombined effect of the BMMSCs and CEE onthe flap survival of a RSF in rats.
Weobserves significant increase in survival part of flap, and blood vesselsections of CEE, CEE+BMMSCs, BMMSCs groups compared to the control group. Further BMMSCs group showed significantdecreases in survival part of flap compared to CEE and CEE+ BMMSCs groups.Moreover TIIMCs (complete degranulation state of MCs) and total number of MCsin BMMSCs group were significantly higher than CEE, CEE+BMMSCs, and control groups.It seems there is a relation exist between significant increased numbers of TIIMCsin BMMSCs group, and also significant decreases of flap survival in this group.
We hypothesized that there was an interaction between degranulated MCs andBMMSCs in the ischemic tissue in BMMSCs groups, and MCs productionsinduced an inhibitory effect on survivalof RSF compared to CEE group.MCs degranulate and discharge some poisonous molecules,and also their granules accumulate several pre-stored mediators, such as histamine and proteases that are secreted fromMCs, and activated by numerous signalpathways. Other investigations established that these mediators participate in dissimilareffects in the development of different illnesses,for example I/R injury(24,25).
Histamine is an important mediator of inflammatory and allergic responses (26). Stabilizing MCs?membrane using Cromolyn sodium inhibiting MC degranulation from secreting media (27). Bycontrast, Compound 48/80(an activator to MCs?membrane, promotes thedegranulation and then aids the secretionof mediators (28). MCs are active in early phase of inflammation ofderma repair(10). However the effects of MC in I/R injury are not completely apparent(29,30).growingfacts recommends that MCs participate an important function in I/R injury (7,8,30) Moreover , I/R injury is explained to be reduced in the geneticallymast-cell deficient rats(31,32) , but there are some exceptions (9,10).Weobserved that rats treated with BMMSCs demonstrated a significant decrease in flap survival compared to CEE and CEE+BMMSCsgroups.
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At the same time, the total number of MCs and degranulted MCs countswere significantly increased in flaps from BMMSCSs group compared CEE -treated andcontrol groups. The administration of CEE after surgery can significantlyreduce the extent of flap necrosis and the total number of MCs and degranulted MCs counts caused byI/R injury. This protective effect is not seen with BMMSCs group.
Theprotective effect of CEE on flapnecrosis might be also related to the decreases in the total number of MCs and degranulted MCs within the flap. Our results probablydemonstrate that degranulted MCs could release some toxins that must mediate a factorof tissue injury. Consistency Yang et al evaluated the role of MCs in hepaticI/R injury. They showed that both thestabilization of MCs with Cromolyn and depletion of MCs with compound 48/80 facilitateprotection against liver damage after I/R injury. Yang et al concludedthat MC degranulation promotes hepaticI/R injury in rats(7).Georgopouloset al investigated whether hydroxyzine can reduce the necrotic area in I/Rinjury in epigastric rat skin flaps and to compare its role with cimetidine andvitamin C.
Georgopoulos et al suggested that administering hydroxyzine in rat epigastric skin flaps beforereperfusion may decrease necrosis, neutrophils and MC counts(8). Cordeiro et alexamined the role of MCs and theirprincipal product, histamine, in I/R injury in an ischemic epigastric islandskin flaps . Cromolynsodium, diphenhydramine, and cimetidine were administered to the flaps. Cordeiro et al evaluated flap survival, MCsand, neutrophil count, andmyeloperoxidase levels.
Cordeiro et al observed that the animals treated withdiphenhydramine and cimetidine demonstrated significant decrease in flapnecrosis. Both neutrophil and MC counts were significantly decreased in flapsfrom antihistamine-treated compare to both control and cromolyn sodium-treatedgroups. Cordeiro et al concluded that the protective effect of antihistamineson flap necrosis might be related to the decrease in neutrophils and, possibly,MCs within the flap (30).Rorket al stated that MCs in the heart contribute to reperfusion injury followingmyocardial ischemia. Since the activation of A2A adenosine receptors (A2AARs)inhibits reperfusion injury, Rork et al hypothesized that ATL146e (a selectiveA2AAR agonist) might protect hearts in part by reducing cardiac MCsdegranulation.
Rork et al suggest that in ex vivo, buffer-perfused hearts, MCsdegranulation contributes to I/R injury. In addition, their data suggest that A2AAR activation iscardioprotective in the isolated heart, at least in part by attenuatingresident MCs degranulation(31).Andoh et al studied the role of mucosal type MCs(MMC) in the development of intestinal I/R in Ws/Ws rats.
Ws/Ws rats have a small deletion of the c-kit gene, andare deficient in both mucosal and connective tissue-type MCs. Andoh et alreported that their results providedirect evidence for the positive role of MCs in the pathogenesis of intestinalischaemia-reperfusion injury(32).Inthis regard most current knowledge about the function of MCs in I/R injuryrelate to degranulation, which correlates strongly with the severity of IRinjury in many organs(30,33,34,35).Shortlyafter I/R, MCs release many chemicals which can cause injury during organ I/Rby degranulating or synthesizing new chemicals(28).
