The expression of TRPM4 protein is increased in the hippocampus of aged PND rats, and ulinastatin affects TRPM4 and apoptosis to enhance cognition dysfunction

Background Transient receptor potential melastatin 4(TRPM4)is a non-selective cation channel that is mainly permeable to Na+, activated by intracellular calcium, and modulated by ATP; Dysregulation of TRPM4 contributes to many pathological processes, including stroke, cerebral edema after traumatic, spinal cord injury and neurodegenerative diseases。TRPM4 plays an important role in neuronal apoptosis and mitochondrial function protection, and we assume that it plays a role in PND. Ulinastatin has been shown to have a protective effect on perioperative neurocognitive function, and we used the group with Ulinastatin as a protective agent for comparison. Methods Forty18-month-old male Sprague-Dawley rats were divided into four groups: group C (sham-operated); surgery group (internal fixation of tibial fracture); UTI group (Ulinastatin + surgery), and 9- phenanthrol group (TRPM4 channel inhibitor + surgery). Western blotting, qPC,and IF were used to detect the expression levels of TRPM4 in different groups of rats. The neurocognitive function of rats was detected by the Y-maze and NOR test. The expression of apoptosis-related proteins in rat hippocampal cells was detected, and the apoptosis level of rat hippocampal cells was detected by the TUNEL method. Mitochondrial morphology was observed by transmission electron microscopy. Results TRPM4 expression was significantly higher in the hippocampus of rats in the surgery group compared with the sham surgery group. Behavioral assays in the 9-phenanthrol group showed better results than those in the surgery group, with decreased expression of BAX, an apoptosis-related protein, elevated expression of BCL-2, and decreased tunel Apoptosis Index in the hippocampus of rats. The Ulinastatin group and the inhibitor group had similar results. Conclusion TRPM4 expression is elevated in the hippocampus of aged PND rats, and inhibition of its expression attenuates hippocampal apoptosis and protects perioperative neurocognitive function in rats, with a similar effect to that of Ulinastatin protection.