The Healing Effect Of Heparin On The Traumatic Tympanic Membrane Perforation In Animal Models

Background:The traumatic tympanic membrane (TM) perforation is a common condition that most patients can be self-healing. But once secondary infection can lead to permane nt tympanic membrane perforation. In recent years, studies have focused on the materials that combined with atelocollagen membrane closing traumatic TM perforation. Recently, more and more biological activity of heparin was found, and its role in normal wound healing is well documented. There are mane groth factor participate during the course of tympanic membrane perforation.The effect of heparin to the TGF-α,bFGF during the course of tympanic membrane perforation has rarely been shown in studies.Objective:To approach the efficacy of local application heparin in the treatment of acute traumatic tympanic membrane perforation (TMP) in the animal models. Methods:①To develop an animal model of traumatic TMP in the rat:50 wistar rats (200-250g) were used. The external auditory of all animals were disinfectioned by 75% alcoholic, then bilateral central perforations were created by excising (2mm X 2mm) of the tympanic membrane with a thermal needle reference to Amoils. To discourage infection, intramuscular injections of ampicillin sodium (150 mg/kg) were given after the operation everyday for a total of five days.②50 rats were randomly divided into two groups:In the first group, right ear was treated by using heparin combined with. Gelfoam pledget which was placed over the TMP in contact with both the TM remnant and medial ear canal wall, and left ear served as blank control. In the second group,the right ear was treated by using heparin combined with Gelfoam pledget, left ear was treated by using EGF combined with Gelfoam pledget.5 rats were killed after 1,3,5,7,10 days in each group, then the temporal bones of every animals were fixed in 10% formalin, sectioned at 4μm,stained with hematoxylin-eosin and examined by immunohistochemical method using polyclonal antibodies of TGF-a, bFGF. Immunohistochemical data were analyzed with paired t test.Results:1. The healing TM using heparin combined with Gelfoam pledget and EGF combined with Gelfoam pledget spend more little time then the blank controled during the time of the wounded area healing. Histology of heparin-healed TM at 5 days is very similar to that of normal both in their overall thickness and in the relative proportions of the three component layers.2. Statistical difference between treated and control ears in the expression of TGF-a,bFGF was evident(p<0.05).Statistical difference between heparin and EGF ears in the expression of TGF-a,bFGF was not evident(p>0.05).Conclusions:1. Heparin can enhance and entend the time of the expression of TGF-a,bFGF in the healing TM perforation.2. These results suggest heparin is effective in enhancing closure of traumatic TMperforation and can shorten the healing time of TMP in the rat model.3. Histology of heparin-healed TM is very similar to that of normal, both in their overall thickness and in the relative proportions of the three component layers.Local application heparin can accelerate the healing of acute traumatic TMP in the animal models.