Dietary Zn proteinate alleviates heat stress-induced intestinal integrity disruption possibly by promoting cell proliferation via related signaling pathways in the jejunum of broilers

Heat stress (HS) can induce the disruption of small intestinal integrity in broilers. Here we examined the efficacies and possible mechanisms of zinc proteinate with moderate chelation strength (Zn-Prot M) compared to ZnSO 4 .7H 2 O (ZnSO 4 ) in alleviating HS-induced disruption of small intestinal integrity in broilers. The experiment included 7 treatments. Twenty two-d-old birds were randomly allotted into 1 of 5 treatments under high temperature (HT, 9:00-17:00: 34±1°C, 8 h d -1 ; 17:00–9:00: 28±1°C) with 1 control (HT-CON) plus 2 [dietary Zn sources, Zn-Prot M and ZnSO 4 ] × 2 [added Zn levels, 30 and 60 mg kg -1 ] factorial arrangement, and 1 of 2 treatments under normal temperature (NT) with the control (NT-CON) and pair-feeding matched to HT-CON (NT-PF). The results showed that HS dramatically reduced ( P <0.05) small intestinal villus height (VH), VH/crypt depth (CD) and villus surface area (VSA), the amount of proliferating cell nuclear antigen (PCNA) positive cells, mRNA or protein expression levels of phosphatidylinositol 3-kinase (PI3K), serine threonine kinase (AKT), extracellular regulated protein kinase (ERK), protein kinase C (PKC), G protein-coupled receptor 39 (GPR39), phosphorylated PI3K (p-PI3K)/PI3K, p-AKT/AKT, p-ERK/ERK and phospholipase C (PLC) β1/2, and PLC activity. HS also remarkably increased ( P <0.05) small intestinal CD and mRNA or protein levels of P38 mitogen activated protein kinase (P38 MAPK), C-jun N-terminal kinase (JNK)1/2 and p-JNK/JNK in the jejunum of heat stressed (HS) broilers. However, dietary supplementation with Zn, especially organic Zn as Zn-Prot M at 60 mg kg -1 , significantly increased ( P <0.05) small intestinal VH, VH/CD and VSA, as well as the amount of PCNA positive cells, PLC activity, mRNA expression levels of PI3K , AKT , GPR39 and PLC β1 , protein expression levels of p-PI3K/PI3K, p-AKT/AKT, p-ERK/ERK, GPR39 and PLC β1, and decreased ( P <0.05) small intestinal CD, JNK2 mRNA expression level and p-JNK/JNK protein expression level in the jejunum of HS broilers. These results suggest that dietary supplemental Zn, especially 60 mg Zn kg -1 as Zn-Prot M, can effectively alleviate HS-induced small intestinal injury possibly by promoting cellular proliferation via the GPR39/PLC β1-mediated PI3K/AKT or MAPK pathways in the jejunum of HS broilers.