解脲支原体感染动物模型优化方案研究

Optimization of animal models of Ureaplasma urealyticum infection

目的探索不同造模方法的优劣性,选择最合适的解脲支原体感染动物模型方法。方法选择SPF级BALB/c雌性小鼠、Wistar大鼠,分别以小剂量UU3菌液多次感染、大剂量UU3菌液一次感染、苯甲酸雌二醇预处理为干预措施,建立解脲支原体感染动物模型,分别于首次接种后14 d、28 d、42 d、56 d取实验动物宫颈分泌物行解脲支原体培养,取生殖器做形态学分析。结果 1BALB/c小鼠与Wistar大鼠相比,BALB/c小鼠总体一般情况较差,阴道分泌物增加,外阴溃烂明显,而Wistar大鼠外阴无明显变化。2大鼠各组阴道UU定植率比较,差异均具有统计学意义(P<0.05);小剂量雌激素组与小剂量非雌激素组比较,差异有统计学意义(P<0.05);大剂量雌激素组与大剂量非雌激素组比较,差异有统计学意义(P<0.05);小剂量雌激素组与大剂量雌激素组比较,差异有统计学意义(P<0.05);小剂量非雌激素组与大剂量非雌激素组比较,差异有统计学意义(P<0.05)。小鼠各组结果同大鼠。3同样干预措施,在小剂量雌激素处理下,大、小鼠比较,差异有统计学意义(P<0.05);在大剂量雌激素处理下,大、小鼠比较,差异有统计学意义(P<0.05),说明同等处理措施下小鼠阴道UU定植率更高。4肉眼观:小剂量雌激素组个别大鼠生殖道组织有水肿,其余各组大鼠生殖道组织柔软,活动度好;空白组小鼠生殖道组织柔软,活动度好;小剂量雌激素组小鼠生殖道组织充血明显,输卵管积水,增粗,僵硬,弹性差;大剂量雌激素组小鼠以疏松水肿为主;小剂量非雌激素组和大剂量非雌激素组仅见阴道、宫颈轻度充血水肿。5镜下观:大鼠各干预组阴道组织无明显病理损伤,部分可见疏松组织水肿。小剂量雌激素组小鼠病理损伤严重;小剂量非雌激素小鼠组、大剂量雌激素小鼠组充血水肿程度较轻,腺体轻度扩张,炎性分泌物较多。结论 BALB/c小鼠与Wistar大鼠相比,外阴损伤明显;雌激素预处理能增加实验动物解脲支原体的定植率;小剂量多次感染比大剂量一次感染更能增加UU定值率;UU在BALB/c小鼠阴道UU定植率更高;BALB/c小鼠病理损伤严重,对动物实验研究价值更大。

Objective To explore different methods for establishing animal models of Ureaplasma urealyticum （UU） infection and to select the best method of establishment of this disease. Methods SPF female BALB/c mice and Wistar rats were multiple-infected with small dose of UU liquid or single-infected with high-dose UU liquid, pretreated withestradiol benzoate, to establish models of Ureaplasma urealyticum infection. Cervical secretion was taken for UU culture at 14, 28, 42 and 56 days after the first time UU treatment, and the reproductive organs were taken for histopathological examination. Results Gross examination of the UU-infected rats showed generally less serious lesions than the mice. The low-dose estrogen group was worst, showing hyperemia and edema, cervical hypertrophy, hydrosalpinx, enlargement, and more rigid with poor elasticity. Significant differences were observed in the vaginal UU colonization rates between the low- dose estrogen and low-dose non-estrogen groups, high-dose estrogen and non-estrogen groups, low-dose estrogen and high- dose estrogen groups, low-dose estrogen and non-estrogen groups, in both the mice and rats （P 〈 0. 05 for all）. The same dose estrogen treatment caused a higher UU colonization rate in the mice than rats （ P 〈 0. 05 ）. Histological examination showed that the low-dose estrogen treated rats had no obvious pathological changes, except loose tissue edema in some rats, but apparent pathological changes were observed in the low-dose estrogen treated mice. Conclusions The vulvar lesions in the mice are worse than in the rats. Estrogen pre-treatment can increase the Ureaplasma urealyticum colonization rate in the animals. The UU colonization rate in the vagina of mice is higher than in the rats, and multiple low-dose UU treatment produces a higher UU colonization rate than a single high-dose UU treatment. Therefore, BALB/c mice are more susceptible to Ureaplasma urealyticum infection, with more serious pathological changes, and are more suitable for experimental studies of related diseases.