目的 探讨多房棘球蚴对肝组织p38MAPK通路的影响及肝组织p38MAPK分子表达水平对多房棘球蚴的作用。 方法 从腹腔内保种的沙鼠取多房棘球蚴原头节，选取4~6周的C57BL/6J小鼠，随机分为感染组、未感染组和抑制组，每组10只。抑制组肝门静脉注射SB202190溶液（5 mg/kg，20%DMSO和80%生理盐水混合溶剂），未感染组和感染组仅注射溶剂，每周注射1次，共4周；感染组和抑制组小鼠开腹手术将500个原头节注射于肝脏被膜下，饲养8周。安乐处死后，取肝脏称重并计算肝重比（肝脏质量/体质量），取邻近（距离囊泡0.3 cm以内）及远离（距离囊泡1 cm以外）多房棘球蚴囊泡的肝组织，用石蜡包埋并切片，进行苏木精-伊红（HE）染色、过碘酸雪夫/糖原（PAS）染色、Masson染色并分析炎性带、肝脏纤维化范围。采用TRIzol法提取肝组织RNA，实时荧光定量PCR（qPCR）检测MAPK14基因的表达水平。取各组邻近多房棘球蚴囊泡肝组织，采用蛋白质免疫印迹（Western blotting）和肝脏组织切片免疫组织化学，检测p38MAPK及p-p38MAPK表达水平。 结果 未感染组肝重比为（6.49 ± 0.19）%，感染组增加至（6.80 ± 0.33）%（t = 2.74，P < 0.05）；未感染组肝体积为（5.27 ± 0.34）cm³，感染组增大至（5.80 ± 0.49）cm³（t = 2.83，P < 0.05）。HE染色结果显示，未感染组无炎性带，感染组和抑制组炎性带面积占比分别为（51.2 ± 14.0）%和（23.8 ± 9.8）%，抑制组与感染组相比肝组织坏死灶减少，炎性带减少（t = 3.92，P < 0.01）。PAS染色结果显示，未感染组、感染组、抑制组紫红色染色区域面积占比分别为（1.3 ± 0.3）%、（7.4 ± 1.8）%、（4.5 ± 0.4）%，抑制组紫红色染色区域相比感染组减少（t = 3.82，P < 0.05）。Masson染色结果显示，未感染组无蓝染区域，感染组、抑制组蓝染区域占比分别为（34.9 ± 4.1）%和（16.3 ± 2.8）%，抑制组蓝染区域与感染组相比明显减少（t = 9.16，P < 0.01）。qPCR结果显示，与远离多房棘球蚴病灶的肝组织（1）相比，感染组邻近病灶肝组织MAPK14相对表达水平为7.14 ± 2.23（t = 6.13，P < 0.01）；与未感染组（1）相比，感染组MAPK14相对表达水平为3.17 ± 0.68（t = 7.14，P < 0.01）。抑制组病灶邻近肝组织MAPK14基因相对表达水平为0.07 ± 0.01，相比感染组表达量（1）明显降低（t = 126.83，P < 0.01）。Western blotting结果显示，未感染组p38MAPK、p-p38MAPK相对表达量及p38MAPK/p-p38MAPK值分别为0.80 ± 0.08、0.67 ± 0.11、0.74 ± 0.09，感染组分别为0.97 ± 0.14、0.87 ± 0.09、0.91 ± 0.14，抑制组分别为0.41 ± 0.07、0.20 ± 0.07、0.49 ± 0.21，抑制组与感染组相比均明显降低（t = 7.97、13.32、3.74，均P < 0.01）。免疫组化结果显示，未感染组、感染组和抑制组p38MAPK评分分别为4（4，4）、6（6，9）、4（2，4）分，p-p38MAPK评分分别为4（4，6）、9（8，9.75）、6（6，6）分，抑制组病灶邻近肝组织p38MAPK和p-p38MAPK的相对分子表达水平与感染组相比均明显降低（Z = -3.00、-3.11，均P < 0.01）。 结论 多房棘球蚴可促进其邻近肝组织p38MAPK的表达及磷酸化，邻近肝组织的p38MAPK信号通路可参与维持多房棘球蚴的生长及侵袭能力。

Objective To investigate the influence of Echinococcus multilocularis on the p38MAPK signaling pathway in liver tissue and the affect of p38MAPK expression level on E. multilocularis metacestodes. Methods E. multilocularis protoscolices were collected from the abdominal cavity of preserved gerbils. C57BL/6J mice aged 4-6 weeks were randomly assigned into three groups as infected group, uninfected group, and inhibitory group, with 10 mice each group. The inhibitory group mice were injected via liver portal vein with SB202190 solution (5 mg/kg, in mixed volvent of 20% DMSO and 80% sterile saline), while the uninfected and infected groups received the solvent only, once a week, for total 4 weeks. Subsequently, both the infected and inhibitory groups were given by liver subcapsular injection with 500 protoscolices and raised for 8 weeks. After euthanasia, the mice livers were collected and weighed to calculate weight ratio (liver mass/ body mass). Liver tissues adjacent to (within 0.3 cm) and distant from (1 cm away) the metacestode vesicles were collected. These liver samples were embedded with paraffin and sectioned, and then stained with hematoxylin-eosin (HE), periodic acid-schiff (PAS), and Masson’s trichrome for analyzing the range of inflammatory bands and hepatic fibrosis. Utilizing the TRIzol method, RNA was extracted from the liver tissues to detect the expression levels of MAPK14 gene by quantitative PCR (qPCR). Subsequently, liver tissues adjacent to the vesicles from each group were examined for the expression levels of p38MAPK and p-p38MAPK using Western blotting and immunohistochemical methods, respectively. Results The livermass/body mass weight ratio in the uninfected group was (6.49 ± 0.19)%, while it was increased to (6.80 ± 0.33)% in the infected group (t = 2.74, P < 0.05). The liver size in the uninfected group was (5.27 ± 0.34) cm³, whereas it increased to (5.80 ± 0.49) cm³ in the infected group (t = 2.83, P < 0.05). HE staining indicated the absence of inflammatory bands in the uninfected group, with the infected and inhibitory groups showing inflammatory band areas of (51.2 ± 14.0)% and (23.8 ± 9.8)%, respectively. The inhibitory group displayed a significant decrease in hepatic necrotic foci and inflammatory bands compared to the infected group (t = 3.92, P < 0.01). PAS staining revealed that the area of purple-red stained regions accounted for (1.3 ± 0.3)% in the uninfected group, (7.4 ± 1.8)% in the infected group, and (4.5 ± 0.4)% in the inhibitory group. The inhibitory group showed a significant reduction in the area of purple-red staining compared to the infected group (t = 3.82, P < 0.05). Masson’s trichrome staining demonstrated an absence of blue-stained areas in the uninfected group, indicative of the absence of collagen deposition. In contrast, the infected and inhibitory groups exhibited blue-stained areas representing (34.9 ± 4.1)% and (16.3 ± 2.8)% of the total tissue area, respectively. The extent of the blue-stained areas was significantly reduced in the inhibitory group compared to the infected group (t = 9.16, P < 0.01). qPCR analysis indicated that the relative expression of MAPK14 in liver tissues adjacent to E. multilocularis lesions in the infected group was significantly higher, with a level of 7.14 ± 2.23 (t = 6.13, P < 0.01), compared to tissues distant from the lesions (1). The infected group also demonstrated an elevated MAPK14 expression level of 3.17 ± 0.68 (t = 7.14, P < 0.01) relative to the uninfected group (1). The inhibitory group displayed a substantial decrease in MAPK14 expression levels adjacent to the lesions, with a relative expression of 0.07 ± 0.01, significantly lower than that of the infected group (1) (t = 126.83, P < 0.01). Western blotting data indicated that the ratio of p38MAPK to its phosphorylated form, p-p38MAPK, was significantly different among the groups. In the uninfected group, the relative expression levels of p38MAPK and p-p38MAPK, as well as p38MAPK/p-p38MAPK values were 0.80 ± 0.08, 0.67 ± 0.11, and 0.74 ± 0.09, respectively. For the infected group, the ratio increased to 0.97 ± 0.14, 0.87 ± 0.09, and 0.91 ± 0.14, respectively. The inhibitory group exhibited a markedly reduced ratio to 0.41 ± 0.07, 0.20 ± 0.07, and 0.49 ± 0.21, respectively, when compared to the infected group (t = 7.97, 13.32, 3.74, all P < 0.01). Immunohistochemical results showed p38MAPK scores of 4 (4, 4) for the uninfected group, 6 (6, 9) for the infected group, and 4 (2, 4) for the inhibitory group. The p-p38MAPK scores were 4 (4, 6), 9 (8, 9.75), and 6 (6, 6), respectively. Compared to the infected group, the inhibitory group exhibited a significant decrease in the molecular expression levels of both p38MAPK and p-p38MAPK in liver tissues adjacent to the lesions (Z = -3.00, -3.11, both P < 0.01). Conclusion E. multilocularis metacestode could promote the expression of p38MAPK and its phosphorylation in the liver tissue adjacent to the vesicles, while the p38MAPK signaling pathway in adjacent liver tissue may involve in maintaining the growth and invasive ability of metacestode.