Effect of locally combined use of sodium hyaluronate and 5-fluorouracil on the tendon adhesion and healing in rabbits

Abstract

Objective To assess the effect of locally combined use of sodium hyaluronate (SH) and 5-fluorouracil (5-Fu) on the tendon adhesion and healing. Methods Ninety mature New Zealand white rabbits (weighing 2.0-2.5 kg, half males and half females) were randomly divided into 3 groups (n=30 each): SH group, 5-Fu group and SH+ 5-Fu group. A tendon injury model was established in the hind legs. In experimental groups, the injured tendons of the right hind legs were given SH (SH group), 5-Fu (5-Fu group) and combined use of SH and 5-Fu (SH+ 5-Fu group) respectively. The injured tendons of the left hind legs were given same volume of normal saline in the control group. The gross and histological changes were examined to observe the adhesion degree and the fibroblast cells at 1st, 3rd and 6th week, respectively. Under the electron microscope, the fibroblast cells and collagenous fibers were observed at 6th week. Results At 1st, 3rd and 6th week, as compared with the control group, the grading of adhesion in the SH group, the 5-Fu group and the SH+ 5-Fu group was significantly decreased, respectively (P=0.048, 0.044, 0.001; 0.036, 0.045, 0.005; 0.035, 0.016, 0.001), and the grading of adhesion in the SH+ 5-Fu group was significantly slighter than that in the SH group and 5-Fu group (P=0.047, 0.019, 0.032; 0.014, 0.019, 0.034). The number of fibroblasts in the tendon parenchyma in the SH+ 5-Fu group (at 1st week: 153.20±13.26; at 3rd week: 192.30±10.94; at 6th week: 195.60±12.93) was significantly greater than in the control group (at 1st week: 64.30±5.60; at 3rd week: 91.60±8.36; at 6th week: 92.90±7.61), the SH group (at 1st week: 94.00±10.67; at 3rd week: 133.10±10.72; at 6th week: 134.80±8.51) and the 5-Fu group (at 1st week: 100.30±10.38; at 3rd week: 139.60±10.27; at 6th week: 141.20±10.97, P=0.018, 0.001, 0.001), respectively. The number of fibroblast cells in the tendon sheath and epitenon in the SH+ 5-Fu group (at 1st week: 103.40±8.34; at 3rd week: 84.40±9.05; at 6th week: 80.00±10.57) was significantly less than that in the control group (at 1st week: 210.80±12.94; at 3rd week: 189.50±15.07; at 6th week: 184.40±15.61), the SH group (at 1st week: 140.30±13.84; at 3rd week: 121.40±13.75; at 6th week: 115.40±14.36) and the 5-Fu group (at 1st week: 147.50±8.15; at 3rd week: 127.20±8.64; at 6th week: 121.50±7.56, P=0.005, 0.007, 0.019), respectively. At 6th week, the fibroblasts and collagenous fibers in the SH+ 5-Fugroup were more regular in structure and arrangement under the electron microscope. Conclusion Combined use of SH and 5-Fu can promote the proliferation of fibroblasts and synthesis of collagenous fibers in the tendon parenchyma, and can reduce the proliferation of fibroblasts and synthesis of collagenous fibers in the tendon epitenon. It can improve the tendon healing and reduce the tendon adhesion. Key words: Sodium hyaluronate; 5-Fluorouracil; Tendon adhesion; Tendon healing; Tendon injury