目的 探讨小鼠白细胞介素-4（IL-4）对肠道期旋毛形线虫感染的保护作用。 方法 消化旋毛虫保种小鼠肌肉，收集肌幼虫，超声破碎后离心，取上清制备旋毛虫抗原。将10只野生型BALB/c小鼠随机分成未感染组和野生感染组，每组5只；另取4只IL-4敲除（IL-4KO）BALB/c小鼠作为IL-4KO感染组。野生感染组和IL-4KO感染组每鼠灌胃旋毛虫肌幼虫400条，未感染组灌胃等体积PBS。感染旋毛虫后8 d，采集各组小鼠眼眶静脉血，离心收集血清，ELISA检测单核细胞趋化因子1（MCP-1）含量。剖取十二指肠和近端空肠，制备石蜡切片后进行苏木精-伊红（HE）染色，使用Aperio ImageScope 12.4.3测量测量十二指肠、空肠的肠绒毛和隐窝的长度与杯状细胞的数量和大小，计算肠绒毛长度/隐窝长度的比值（V/C）和杯状细胞数/绒毛长度的比值（GC/V）。分离肠系膜淋巴结中的淋巴细胞，与旋毛虫抗原（10 μg/ml）共培养72 h，收集细胞上清，高通量液相蛋白芯片（Luminex）技术检测IL-1β、IL-12p70、IL-2、IL-5、IL-6、干扰素γ（IFN-γ）、肿瘤坏死因子α（TNF-α）的含量。使用SPSS 26.0统计软件对数据进行分析，两两比较采用独立样本t检验，多样本比较采用单因素方差分析。 结果 ELISA结果显示，未感染组、野生感染组、IL-4KO感染组小鼠血清中MCP-1含量分别为（344.90 ± 21.80）、（350.50 ± 38.30）、（467.94 ± 190.01）pg/ml，IL-4KO感染组高于野生感染组（t = 0.681，P < 0.05）。HE染色结果显示，未感染组小鼠的十二指肠和空肠肠黏膜完整、绒毛结构正常，无炎症改变；野生感染组、IL-4KO感染组小鼠的十二指肠和空肠肠黏膜均出现空泡状的杯状细胞、绒毛长度变短，炎症明显，IL-4KO感染组炎症更为严重。IL-4KO感染组小鼠十二指肠和空肠V/C分别为2.62 ± 0.12、2.78 ± 0.25，均低于野生感染组的3.46 ± 0.05、3.65 ± 0.12（F = 24.09、20.46，P < 0.01、0.05）；未感染组空肠V/C为4.69 ± 0.16，高于野生感染组（F = 25.43，P < 0.01）。IL-4KO感染组十二指肠和空肠GC/V分别为9.66 ± 0.88、7.33 ± 0.88，均高于野生感染组的5.33 ± 1.20、4.33 ± 0.33（F = 17.12、16.78，均P < 0.05）。IL-4KO感染组十二指肠和空肠杯状细胞大小分别为（12.39 ± 1.17）、（11.05 ± 0.60）μm，均大于野生感染组的（8.33 ± 0.44）、（8.44 ± 0.58）μm（F = 18.47、16.22，均P < 0.05）。Luminex结果显示，野生感染组小鼠淋巴细胞培养上清中IL-1β、IL-12p70、IL-2、IL-5、IL-6、IFN-γ、TNF-α的含量分别为（0.45 ± 0.03）、（1.03 ± 0.04）、（1.00 ± 0.38）、（0.64 ± 0.16）、（0.62 ± 0.24）、（0.57 ± 0.09）、（0.94 ± 0.31）pg/ml，IL-4KO感染组的含量分别为（0.80 ± 0.37）、（2.70 ± 0.94）、（49.76 ± 16.40）、（25.25 ± 3.26）、（12.51 ± 4.86）、（51.20 ± 8.93）、（15.86 ± 2.74）pg/ml；除IL-1β（F = 0.87，P > 0.05）外，IL-4KO感染组均高于野生感染组（F = 5.52、24.73、48.72、5.00、123.10、50.55，P < 0.05或0.01）。 结论 IL-4在旋毛虫感染肠道期起免疫保护作用，能够降低小鼠血清中MCP-1含量，减缓十二指肠及空肠的炎症反应，抑制炎性细胞因子的分泌。

Objective To investigate the protective effects of interleukin 4 (IL-4) to Trichinella spiralis infection in the intestinal phase in mice. Methods The muscle samples of T. spiralis reservation mice were digested for collection of muscle larvae, which were sonicated and centrifuged to collect supernatant for preparing Trichinella antigen. Ten wild-type BALB/c mice were randomly divided into the non-infection group and wild-type infection group, with 5 mice each group, while additional 4 IL-4 knockout mice (IL-4KO) were assigned to IL-4KO infection group. The mice of wild-type infection group and IL-4KO infection group were given with 400 muscle larvae each by gavage respectively, while the non-infection group received the same volume of PBS. Eight days after infection, orbital blood samples were obtained to collect sera by centrifugation, and the content of monocyte chemotactic protein-1 (MCP-1) was detected by ELISA. The mice of all groups were dissected to collect the duodenum and proximal jejunum for preparation of paraffin sections. The sections were stained with Hematoxylin and eosin (HE). Measure the length of villi and crypts as well as the number and size of goblet cells useing Aperio ImageScope 12.4.3, and calculate the villus length/crypt length (V/C) and the ratio of the number of goblet cell/villus length (GC/V). Lymphocytes isolated from the mesenteric lymph nodes were cultured with Trichinella antigen (10 μg/ml) for 72 hours, and the supernatant was collected. A Luminex assay was performed to measure the levels of cytokines including IL-1β, IL-12p70, IL-2, IL-5, IL-6, interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α). The data was analyzed using SPSS 26.0 software with independent sample t-tests for pairwise comparisons and one-way ANOVA for multiple sample comparisons. Results ELISA results showed that serum MCP-1 levels were (344.90 ± 21.80), (350.50 ± 38.30) and (467.94 ± 190.01) pg/ml in the non-infection, wild-type infection and IL-4KO infection group, respectively, the IL-4KO infection group was higher than the wild-type infection group (t = 0.681, P < 0.05). HE staining revealed intact mucosa and normal villous architecture with no signs of inflammation in the non-infection group, whereas both the wild-type infection and IL-4KO infection groups showed vacuolated goblet cells, shortened villi and marked inflammation in the duodenum and jejunum, with more severe inflammation in the IL-4KO infection group. The IL-4KO infection group had V/C of 2.62 ± 0.12 and 2.78 ± 0.25 in the duodenum and jejunum, which were both lower than those in the wild-type infection group (3.46 ± 0.05, 3.65 ± 0.12) (F = 24.09, 20.46, P < 0.01, 0.05). The non-infection group had higher V/C of 4.69 ± 0.16 in the jejunum (F = 25.43, P < 0.01). The IL-4KO infection group had GC/V of 9.66 ± 0.88 and 7.33 ± 0.88 in the duodenum and jejunum, which were both higher than those in the wild-type infection group (5.33 ± 1.20 and 4.33 ± 0.33) (F = 17.12, 16.78, both P < 0.05). The goblet cell size in the duodenum and jejunum of the IL-4KO infection group were (12.39 ± 1.17) and (11.05 ± 0.60) μm, both larger than the wild-type infection group, which had (8.33 ± 0.44) and (8.44 ± 0.58) μm (F = 18.47, 16.22, both P < 0.05). The Luminex results showed that the levels of IL-1β, IL-12p70, IL-2, IL-5, IL-6, IFN-γ and TNF-α in the lymphocyte culture supernatants of the IL-4KO infection group were (0.80 ± 0.37), (2.70 ± 0.94), (49.76 ± 16.40), (25.25 ± 3.26), (12.51 ± 4.86), (51.20 ± 8.93), (15.86 ± 2.74) pg/ml, whereas the wild-type infection group had levels of (0.45 ± 0.03), (1.03 ± 0.04), (1.00 ± 0.38), (0.64 ± 0.16), (0.62 ± 0.24), (0.57 ± 0.09), (0.94 ± 0.31) pg/ml, respectively. The IL-4KO infection group were higher than the wild-type infection group (F = 5.52, 24.73, 48.72, 5.00, 123.10, 50.55, P < 0.05 or 0.01) except IL-1β (F = 0.87, P > 0.05). Conclusion IL-4 plays a protective immunological role during the intestinal phase of T. spiralis infection in mice. It could reduce the serum MCP-1, mitigate inflammation response in the duodenum and jejunum and suppress the secretion of inflammatory cytokines.