Cadmium (Cd) is a toxic environmental pollutant and induces toxic effects to organism. Nevertheless, the mechanism of Cd-induced toxicity in swine remains obscure. To explore this, 10 healthy 6-week-old weaned swine were placed into two groups stochastically, the Cd group was treated with a commercial diet containing 20 mg/kg Cd for 40 days. The results of histopathological and ultrastructural observations showed typical necrosis features and inflammatory cell infiltration in Cd group. Excessive Cd suppressed T-AOC and SOD activities, increased MDA content and ROS levels. Cd diet elevated the expression of RIPK1, RIPK3, and MLKL to activate the RIPK3-dependent necroptosis pathway. Results of Th1 and Th2 cytokines indicated that the levels of IL-4, IL-6 and IL10 was increased, while the level of IFN-γ was decreased, illustrating Th1/Th2 immune imbalance leads to aggravate inflammatory responses. Cd activated the TNF-α/NF-κB pathway and induced inflammatory responses via increasing the expression of HO-1, IL-1β, iNOS, COX2. Heat shock proteins were notably elevated in response to inflammatory reactions. And these effects were inhibited by necrostatin-1 (Nec-1) and N-acetyl-cysteine (NAC). Altogether, these data demonstrated that Cd induced necroptosis and inflammation to aggravate small intestine injury in swine by increasing the excessive accumulation of ROS and imbalanced Th1/Th2, respectively.

镉 (Cd) 是一种有毒的环境污染物，会对生物体产生毒性作用。然而，Cd 对猪的毒性机制仍不清楚。为了探索这一点，将 10 头健康的 6 周龄断奶猪随机分为两组，Cd 组用含有 20 mg/kg Cd 的商业饲料处理 40 天。组织病理学和超微结构观察结果显示 Cd 组有典型的坏死特征和炎症细胞浸润。过量的 Cd 会抑制 T-AOC 和 SOD 活性，增加 MDA 含量和 ROS 水平。Cd 饮食提高了 RIPK1、RIPK3 和 MLKL 的表达以激活依赖于 RIPK3 的坏死性凋亡途径。Th1和Th2细胞因子结果表明IL-4、IL-6和IL10水平升高，而IFN-γ水平降低，说明 Th1/Th2 免疫失衡导致炎症反应加剧。Cd 激活 TNF-α/NF-κB 通路并通过增加 HO-1、IL-1β、iNOS、COX2 的表达诱导炎症反应。响应炎症反应，热休克蛋白显着升高。这些作用被 necrostatin-1 (Nec-1) 和 N-乙酰半胱氨酸 (NAC) 抑制。总之，这些数据表明，Cd 分别通过增加 ROS 的过度积累和 Th1/Th2 的失衡来诱导坏死性凋亡和炎症，从而加重猪的小肠损伤。这些作用被 necrostatin-1 (Nec-1) 和 N-乙酰半胱氨酸 (NAC) 抑制。总之，这些数据表明，Cd 分别通过增加 ROS 的过度积累和 Th1/Th2 的失衡来诱导坏死性凋亡和炎症，从而加重猪的小肠损伤。这些作用被 necrostatin-1 (Nec-1) 和 N-乙酰半胱氨酸 (NAC) 抑制。总之，这些数据表明，Cd 分别通过增加 ROS 的过度积累和 Th1/Th2 的失衡来诱导坏死性凋亡和炎症，从而加重猪的小肠损伤。