Inflammatory reaction is one of the most common renal dysfunction in broilers during production. there is no reliable drug prevention and treatment and the prognosis is poor. NF-κB signaling pathway is one of the most important mechanisms leading to renal injury. SMPs has anti-inflammatory effect, can reduce the inflammatory response of a variety of diseases, and has the effect of inhibiting the inflammatory signal pathway. Studies have shown that SMPs can inhibit the expression of NF-κB induced by oxidative stress and reduce LPS-induced liver injury. Based on the above mechanisms, this study was conducted to investigate whether SMPs has protective effects on kidney injury in broilers, and whether its protective effects on kidney injury in broilers are mediated by inhibition of NF-κB signaling pathway？
In this study, a broiler model with kidney injury was successfully established by drinking 0.15 g/L FFC mixed water for 5 days. Previous studies found that FFC exposure significantly inhibited the growth performance of broilers. (Han et al. 2021). Compared with model group, SMPs dosage groups increased the daily gain of broilers in different degrees. In addition, there was no difference between the control group and the SMPs control group, but the standard deviation was smaller, indicating that the growth difference of the chicken group was smaller, and it was more suitable for collective breeding. A large number of Traditional Chinese medicine polysaccharides were found to have the effect of promoting weight gain. Studies have shown that APS can increase body weight, feed conversion rate and digestive enzyme activities of broilers. (Wu. 2018.). SMWP-U&E can improve digestion and nutrient absorption of weaned piglets, and have beneficial effects on intestinal morphology and microbiota (Jiang et al. 2020). Therefore, we found that SMPs can promote the growth of broilers.
The kidney has the function of circulation and excretion, and is the target organ of poisons (Rubatto Birri et al. 2010). Exposure to FFC causes microscopic changes in renal tissue, including congestion, swelling, and tubular shape. This is consistent with previous research. (Wang et al. 2021) Cr, UA and BUN are commonly used to assess the progression of kidney disease. Anhydride is a chemical waste produced by muscles breaking down a compound called creatinine. As the blood passes through the kidneys, Cr is filtered and excreted in the urine (Baum et al. 1975). Elevated serum Cr level suggests impaired glomerular filtration function in broilers. Wang et al. found that FFC can cause the increase of serum BUN in chickens and then cause kidney injury. Our results are consistent with previous research results (Wang et al. 2021). Renal uric acid excretion is determined by the balance between uric acid reabsorption and resecretion (Bobulescu et al. 2012). High protein diet can increase serum UA levels and cause kidney damage in chickens (Guo et al. 2005). BUN is the end product of protein metabolism in the body. If renal parenchyma is damaged and glomerular filtration rate drops to the critical point, the level of BUN in the blood will increase. In this experiment, the serum Cr, UA and BUN of broilers was significantly increased. These results suggest that FFC exposure has a negative effect on kidney growth and causes kidney damage in chickens. The results showed that different doses of SMPs could improve the kidney injury induced by FFC, and reduce the levels of Cr and BUN in broilers with kidney injury. With the increase of SMPs, the levels of Cr and BUN decreased more obviously. At the same time, SMPs can improve the pathological changes of renal tubules in broilers with kidney injury. Under light microscope, the kidney injury of broilers pretreated with different doses of SMPs was significantly improved, and with the increase of SMPs, the kidney of control group was more likely. The results showed that SMPs could reduce the kidney injury induced by FFC. In addition, SMPs has no negative effects on the kidneys.
Nuclear factor-kB (NF-κB) is a transcription factor that regulates immune and inflammatory responses under various conditions and plays a key role in inflammation and immune responses (Morgan and Liu 2011; Oeckinghaus et al. 2011) The activation of NF-κB is mainly divided into normative pathway and non-normative pathway. Typical pathways are induced by most physiological NF-κB stimuli, such as cytokine receptors, antigen receptors, and pattern recognition receptors. This pathway depends on the catalytic activities of IκKβ and mainly leads to the phosphorylation of IκBα and the nuclear translocation of most heterodimer containing p65.In this study, we found that FFC-induced renal injury promoted NF-κB phosphorylation and expression level of IκBα protein degradation. IκBα is the main protein that activates NF-κB.NF-κB is isolated from the cytoplasm by direct interaction with inhibitor proteins of the IκB family, such as IκBα. IκBα phosphorylation and degradation are critical for NF-κB activation, leading to rapid translocation of NF-κB from cytoplasm to nucleus (Viatour et al. 2005). These results suggest that the activation of NF-κB may be the cause of renal inflammation in broilers. However, the expression of NF-κBp65 and IκKβ in the renal tissue of FFC-induced acute kidney injury model could be inhibited by different doses of SMPs, and the inhibition effect was more obvious with the increase of dose. Studies have shown that SMPs can inhibit IKBα degradation, down-regulate the nuclear translocation of NF-κB, and play an anti-inflammatory role in liver injury in RAW264.7 Cells (Han et al. 2018). This study suggests that the protective effect of SMPs on FFC-induced nephrotoxicity in broilers may be related to the reduction of NF-κB activation.
The expression level of NF-κB can directly affect the transcription of proinflammatory factors. Over-activation of proinflammatory factors can induce the strong expression of TNF-α, IL-6 and ICAM-1, thereby promoting multi-organ cytotoxicity (Wen et al. 2020).Complex inflammation is regulated by a network of cytokines and is evidenced by the production of many pro-inflammatory markers, IL-6, IL-1β, and TNF-α.Some studies have found that renal injury in broilers is associated with excessive release of pro-inflammatory factors (TNF-α, IL-1β, IL-6) (Wang et al. 2017).In this study, it was found that the levels of TNF-α, IL-1β, IL-6 and other inflammatory factors in the kidney of broilers in the model group increased significantly. SMPs can reduce the overexpression of TNF-α, IL-1β and IL-6. This is consistent with whose research results (Han et al. 2018). The results showed that different doses of SMPs could significantly increase the expression of IκBα protein, reduce the expression of IκKβ protein and p65 protein into the nucleus of kidney tissue of broilers, and reduce the production of TNF-α, IL-1β, IL-6 and other pro-inflammatory factors, so as to alleviate the renal injury induced by FFC. This was consistent with a decrease in TNF-α, IL1β, and IL-6 levels in the kidney. Through the above studies, it was preliminarily concluded that the mechanism of SMPs inhibiting the production of pro-inflammatory factors TNF-α, IL-1β, IL-6 and alleviating renal injury might be related to the inhibition of NF-κB signaling pathway.