饲服环磷酰胺对兔耳早期增生性瘢痕组织的影响

Effect of feeding eyclophosphamide on rabbit ears hypertrophic scar tissue in early stage

目的通过饲服环磷酰胺观察其对兔耳早期瘢痕的影响，以探讨临床应用口服免疫抑制剂防治早期瘢痕的可行性。方法以32只新西兰白兔兔耳建立增生性瘢痕动物模型，并将其随机分成4组，即蒸馏水组（A组）、5mg·kg^-1·d^-1环磷酰胺组（B组）、10mg·kg^-1·d^-1组（C组）及30mg·kg^-1·d^-1（D组）。在制作模型前及灌胃后14、28d时分别采血观察白细胞、淋巴细胞变化。28d时取组织HE染色、VG染色法观察瘢痕增生指数（H1）、成纤维细胞密度（NA）、胶原纤维面密度（AA）数值变化。各组数据（HI、NA、AA）比较采用方差分析，方差不齐时作秩和检验。结果14d时，A、B、c、D组白细胞数量分别为（8．62±0．58）×10^9／L、（4．48±0．41）×10^9／L、（2．7±0．26）×10。／L、（1．33±0．27）×10^9／L，淋巴细胞数量分别为（3．11±0．21）×10^9／L、（1．67±0．16）x10^9／L、（0．42±0．10）×10^9／L、（0．40±0．09）×10^9／L；28d时，A、B、c、D组白细胞数量分别为（8．63±0．53）×10^9／L、（5．10±0．27）×10^9／L、（3．10±0．26）×10^9／L、（1．98±0．20）×10^9／L，淋巴细胞数量分另0为（3．06±0．16）×10^9／L、（2．08±0．14）×10^9／L、（0．96±0．19）×10^9／L、（0．14±0．07）×10^9／L，实验各剂量组（B、C、D组）白细胞数量和淋巴细胞数量下降，且随药物剂量的增加而下降更明显，呈负相关，各组间比较差异有统计学意义（P〈0．05）。A、B、C、D组HI值分别为3．02±0．24、2．59±0．43、2．06±0．19、1．63±0．11，AA值分另0为40．49±2．07、35．29±1．99、28．36±1．87、24．99±1．82，NA值分别为4570．5±259．3、4222．5±199．6、3540．3±170．3、3341．4±228．8，对照组与实验各剂量组的HI、AA、NA数值之间比较差异有统计学意义（P〈0．01），且随剂量的增加，除NA值c和D组比较差异无统计学意义外，其余实验各剂量组HI、AA、NA值变小更明显，呈负相关，各组之间比较差异有统计学意义（P〈0．05）。结论饲服环磷酰胺在抑制白细胞和淋巴细胞的同时能明显抑制瘢痕增生，对兔耳早期增生性瘢痕有明显的防治作用。

Objective To investigate the feasibility of prevention and treatment of early scar through observing the effect of feeding immunosuppressive drug cyclophosphamide on rabbit ears hypertrophic scar tissue in early stage. Methods Thirty-two Rabbit ears were used to establish animal models for hypertrophic scar and randomly divided into four groups ： group of distilled water （A） , group of cyclophosphamide5 mg·kg^-1·d^-1（B）, group of 10 mg·kg^-1·d^-1（c）, group of 30 mg·kg^-1·d^-1（D）. Before animal models were built and after administration for 14 days, 28 days, leukocytcs and lymphocytes were detected. After 28 days, specimens were harvested and underwent HE staining and VG staining in order to assess HI, NA, AA value changes. The data （HI, NA, AA） from each group were compared by analysis of variance, and the variance for the rank sum test when missing. Results On the 14th day, the number of leukocytes in group A,B,C,D were （8.62 ±0.58） ×10^9/L, （4.48 ±0.41 ） ×10^9/L, （2.7 ±0. 26）×10^9/L, （ 1.33 ±0. 27） ×10^9/L; the number of lymphocytes in group A, B, C, D were （3. l 1 ±0.21 ） ×10^9/L, （ 1.67 4± 0. 16） × 10^9/L, （0.42 ±0.10） ×10^9/L, （ 0. 40 ± 0.09 ）×10^9/L. On the 28th day, the number ofleukocytes in group A,B,C,D was （8.63 ±0.53） ×10^9/L,（5. 10-±0.27） ×10^9/L, （3. 10 ±0.26） ×10^9/L, （ 1.98 ± 0.20） ×10^9/L; the number of lymphocytes A, B, C, D was （3.06 ± 0. 16） ×10^9/L, （2.08 ± 0. 14） ×10^9/L, （0. 96 ± 0. 19 ） ×10^9/L, （0. 14 ± 0. 07 ） ×10^9/L. On the 14th day and 28th day, the number of leukocytes and lymphoeytes in experimental groups was reduced, showing a negative relation with cyelophosphamide dose （ P 〈 0.05 ）. The HI in group of A, B, C, D was 3.02 ± 0.24,2.59 ±0.43,2.06 ± 0. 19,1.63 ±0. 11 ; the AA was 40. 49 ± 2.07,35.29± 1.99,28.36 ± 1.87, 24.99 ± 1.82; the NA was 4570.5 ± 259.3,4222.5 ± 199.6,3540.3 ± 170.3,3341.4 ± 228.8. The difference in HI, AA, NA between control group and any of the experimental groups was statistically significant （P 〈0.01 ）. Each group, with the dose increased, except NA content of group C and D, the HI, AA, NA was more smaller, negative correlation, the difference was statistically significant（ P 〈 0.05）. Conclusions Feeding cyclophosphamide can inhibit leukocytes and lymphocytes number, so as to inhibit the proliferative activity of hypertrophic scar. It has significant effect on prevention of hypertrophic scar on rabbit ears in early stage.