209-OR: DJB Surgery Improves Oxidative Stress and Alleviates Neuron Cell Injury of Hypothalamus in T2DM Rats by Nrf2/HO-1 Signal

Abstract

Metabolic surgery has become an effective treatment for type 2 diabetes mellitus (T2DM). T2DM is often accompanied with impaired glucose utilization and energy metabolism in the brain, leading to oxidative stress, neuron cells injury and inflammation. Previous studies showed that duodenal jejunal bypass (DJB) surgery significantly improves brain glucose metabolism in T2DM rats. This study investigated the protective effect and regulatory mechanism of DJB surgery on T2DM induced brain injury. In this study, differential expression of hypothalamic proteins and genes was analyzed by protein microarray, Flow cytometry, qRT-PCR, western blot and immunofluorescence. The protein microarray results showed that there were significant differences in the expression of hypothalamic hormone and redox regulation-related proteins between the T2DM-DJB rats and the T2DM-Sham rats. Western blot, qRT-PCR, and immunofluorescence results showed DJB surgery significantly down-regulated the expressions of GFAP, NF-κB, p-NF-κB, IL-1β and IL-6 in the hypothalamus of T2DM rats, and reduces hypothalamic inflammation and glial cell proliferation. DJB surgery up-regulated the expression of C-fos, Ki67, BCL-2 and BDNF, and down-regulated the expression of Caspase-3, Cleaved caspase-3 in the hypothalamus of T2DM rats, which played a neuroprotective role, and reduced the damage of hypothalamus cells. DJB surgery up-regulated the expression of Nrf2 and HO-1 in the hypothalamus of T2DM rats and reduces oxidative stress. Those results indicated that DJB surgery improves hypothalamic inflammation and alleviates neuron cells injury in T2DM rats by activating Nrf2/HO-1 mediated antioxidant signaling. Key words: DJB surgery; T2DM; Apoptosis; Inflammatory; Oxidative stress. Disclosure H.Wang: None. Q.Yan: None. M.Qu: None. Funding National Natural Science Foundation of China (82070856); Shandong Provincial Medicine and Health Commission (202102040075); Weifang Science and Technology Bureau (2021YX071)