重组干扰素联合抗生素对宫颈上皮内瘤变LEEP术后HPV-DNA负荷量及Caspase-3、survivin表达的影响

目的观察重组人干扰素α-2b阴道泡腾胶囊联合头孢拉定胶囊对宫颈上皮内瘤变(CIN)患者宫颈电环切除术(LEEP)后人乳头状瘤病毒(HPV) DNA负荷量及天冬氨酸特异性半胱氨酸蛋白酶3 (Caspase-3)、生存素(survivin)蛋白表达的影响。方法选取2016年10月-2018年10月海南省人民医院妇科收治的CIN患者180例作为研究对象,CINⅠ级、CINⅡ级患者各90例,按照随机数字表法将CINⅠ级患者分为CINⅠA组、CINⅠB组、CINⅠC组,CINⅡ级患者分为CINⅡA组、CINⅡB组、CINⅡC组,各30例。CIN患者均接受LEEP治疗,CINⅠA组及CINⅡA组术后均口服抗生素头孢拉定胶囊,CINⅠB组及CINⅡB组术后均给予重组人干扰素α-2b阴道泡腾胶囊阴道给药,CINⅠC组及CINⅡC组给予口服头孢拉定胶囊联合重组人干扰素α-2b阴道泡腾胶囊阴道给药。观察各组患者临床疗效,术后6个月HPV转阴率,术前、术后6个月HPV-DNA负荷量及宫颈组织中Caspase-3蛋白、survivin蛋白阳性率。结果 CINⅠC组治愈率显著高于CINⅠA组、ⅠB组(χ2=4.216,P=0.040);CINⅡC组治愈率明显高于CINⅡA组、ⅡB组(χ2=6.585,P=0.037)。术后6个月各组患者HPV-DNA负荷量均明显少于术前(P均<0.001),且C组明显少于A组、B组(FCINⅠ=84.294,P<0.001;FCINⅡ=82.601,P<0.001)。术后6个月CINⅠC组患者HPV转阴率为93.3%,明显高于CINⅠA组的73.3%和CINⅠB组的70.0%(χ2=6.634,P=0.036),CINⅡC组为83.3%,显著高于CINⅡA组的60.0%和CINⅡB组的56.7%(χ2=6.104,P=0.047)。术后6个月各组患者Caspase-3、survivin蛋白阳性率均显著低于术前,且C组显著低于A组、B组(Caspase-3蛋白阳性率:χCINⅠ2=5.079,P=0.024;χCINⅡ2=4.286,P=0.038。survivin蛋白阳性率:χCINⅠ2=5.963,P<0.001;χCINⅡ2=4.295,P=0.040)。结论CIN患者LEEP术后联合使用重组人干扰素α-2b阴道泡腾胶囊和头孢拉定胶囊效果明显优于单独应用,不仅可有效减少HPV-DNA负荷量,促进HPV转阴,还能明显降低Caspase-3、survivin蛋白阳性率。

The effect of recombinant interferon combined with antibiotics on the levels of DNA load of HPV and the expression of Caspase-3 and survivin after LEEP for cervical intraepithelial neoplasia

Objective To observe the effect of recombinant human interferon α-2 b vaginal effervescent capsule combined with Cefradine Capsule on the DNA load of human papillomavirus(HPV)and the expression of Caspase-3 and survivin protein in patients with cervical intraepithelial neoplasia(CIN) after LEEP.Methods From October 2016 to October 2018,180 cases of CIN patients admitted to the Department of Gynecology of Hainan People’s Hospital were selected as the research objects,90 cases of CIN class Ⅰ and 90 cases of CIN class Ⅱ respectively.According to the method of random number table,patients with CIN Ⅰ were divided into CIN Ⅰ a group,CIN Ⅰ B group and CIN Ⅰ C group.Patients with CIN Ⅱ were divided into CIN Ⅱ a group,CIN Ⅱ B group and CIN Ⅱ C group with 30 cases each.All patients with CIN were treated with LEEP,Cefradine capsule was taken orally after operation in CIN Ⅰ a group and CIN Ⅱ a group,recombinant human interferon α-2 b vaginal effervescence capsule was given vaginally in CIN Ⅰ B group and CIN Ⅱ B group,Cefradine capsule combined with recombinant human interferon α-2 b vaginal effervescence capsule was given vaginally in CIN Ⅰ C group and CIN Ⅱ C group.To observe the clinical effect of each group,the negative rate of HPV,the DNA load of HPV and the positive rate of caspase3 protein and survivin protein in cervical tissue before and 6 months after operation.Results The cure rate of CIN Ⅰ C group was significantly higher than that of CIN Ⅰ A and IB groups(χ2=4.216,P=0.040);the cure rate of CIN Ⅱ C group was significantly higher than that of CIN Ⅱ A and Ⅱ B groups(χ2=6.585,P=0.037).At 6 months after surgery,the HPV DNA load in each group was significantly less than before surgery(P <0.001),and group C was significantly less than those in groups A and B(FCIN Ⅰ=84.294,P <0.001;FCIN Ⅱ=82.601,P <0.001).At 6 months after surgery,the HPV negative rate of patients in the CIN Ⅰ C group was 93.3%,which was significantly higher than 73.3% in the CIN Ⅰ A group and 70.0% in the CIN Ⅰ B group(χ2=6.634.P=0.036),and 83.3% in the CIN Ⅱ C group.It was significantly higher than 60.0 % in CIN Ⅱ A group and 56.7% in CIN Ⅱ B group(χ2=6.104.P=0.047).The positive rates of Caspase-3 and survivin protein in all groups were significantly lower than those before surgery at 6 months after operation,and the C group was significantly lower than those in Group A and B(Caspase-3 protein positive rate:χ2 CIN Ⅰ=5.079,P=0.024;χ2 CINⅡ=4.286.P=0.038.Survivin protein positive rate:χCIN Ⅰ2=5.963,P <0.001;χCIN Ⅱ2=4.295,P=0.040).Conclusion The combined use of recombinant human interferon α-2 b vaginal effervescent capsule and Cefradine capsule after LEEP for CIN patients is better than that of single application,which can not only effectively reduce the load of HPV-DNA,promote the conversion of HPV to negative,but also significantly reduce the positive rate of Caspase-3 and survivin protein.