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Obstructive jaundice (OJ) is a common clinical pathological syndrome in hepatobiliary surgery. High incidence of multiple organ injuries during perioperative period and its associated mortality remains challenging in clinical practice. Omega-3 polyunsaturated fatty acids (ω-3 PUFA) is an important enteral immune nutrition. This study investigated the protective role of ω-3 PUFA in the regulation of inflammatory response in OJ.Seventy-two rats were randomly divided into obstructive jaundice (OJ) group, obstructive jaundice + ω-3 PUFA group (OJPUFA) group, and sham group. OJ model was created by ligation of the bile duct. Abdominal thoracic catheter was placed to collect lymph. Body weight, liver function, serum and lymphatic levels of TNF-α, IL-1β, IL-10, HMGB1, and nitric oxide (NO) were measured on day 3, day 7, and day 14 after operation. Hematoxylin staining and Alcian blue-periodic acid-Shiff (AB-PAS) staining were performed on the ileum tissue. Protein and mRNA expression of HMGB1, TLR4, and NF-κB p65 were measured at the aforementioned time points.The general condition, including body weight and liver function, were worse in the OJ and the OJPUFA group compared to that in the sham group. On day 14, the body weight recovery and liver function were significantly better in the OJPUFA group than those in the OJ group were (p0.05 for all). No marked change in the serum and lymphatic levels of TNF-α, IL-1β, IL-10, HMGB1 and NO was observed in the sham group after operation, while corresponding levels in the OJ and the OJPUFA groups were significantly higher. Compared with the OJPUFA group, serum and lymphatic levels of the above factors were consistently higher in the OJ group and were significantly higher on day 14 (p0.05 for all). At the same time, ω-3 PUFA lowered the damage of intestinal villi and intestinal mucosal epithelium. It also improved the number and function of goblet cells in intestinal mucosal epithelium. The protein and mRNA expression of HMGB1, TLR4, and NF-κB p65 were significantly higher in the OJ group than those in the OJPUFA group (p0.05 for all).ω-3 PUFA has protective effect in the management of obstructive jaundice. It can regulate the inflammatory response and reduce its damage to intestinal structure. Reducing the activation of HMGB1/TLR4/ NF-κB pathway might be a mechanism for its protective effect. We suggested that ω-3 PUFA and drugs targeted HMGB1/TLR4/NF-κB pathway might be potential treatment strategies in obstructive jaundice.

Several lines of evidence indicate that reactive oxygen species (ROS) overproduction under the metabolic syndrome condition is the leading cause of cardiovascular events. Calcium is an important stimulus for vasoconstriction and plays a pivotal role in the development of hypertension. Here, we investigate whether a relationship exists between metabolic syndrome-induced mitochondrial ROS overproduction and Ang II-mediated Ca2+ release in vascular smooth muscle cells (VSMC). The effect of mitochondrial ROS on AT1 expression, and Ca2+ and IP3 generation was studied in 2 VSMC models of metabolic syndrome using fura-2/AM probes and ELISA-based assay. Ang II-mediated aortic ring contraction in SD rats fed with high-fat diet (HFD) was measured using a force transducer connected to chart recorder. In the metabolic syndrome, almost 2-fold increased mitochondrial O2 - significantly upregulated AT1 expressions by ~60%, companied by elevated Ca2+ and IP3 levels in VSMC and enhanced aortic rings contraction. All these increments were blocked by rotenone (inhibitor of mitochondrial respiratory chain complex I), ruthenium red (inhibitor of calcium uniporter), cyclosporin A (inhibitor of mitochondrial permeability pore), and N-acetylcysteine. Therefore, in the states of metabolic syndrome, ROS overproduction in mitochondrial complex I enhances Ang II-mediated vascular contraction via an AT1-dependent pathway. In addition, the import of Ca2+ from endoplasmic reticulum to mitochondria via calcium uniporter and mitochondrial permeability pore seems to serve as a mechanism to further aggravate mitochondrial damage and vascular dysfunction that may contribute to the occurrence of hypertension.