糖尿病周围神经病变(DPN)是由多种因素引起的,包括反应性自由基(ROS)诱导的过量Ca2流入。瞬时受体电位(TRP)香草素4(TRPV4)是Ca2可渗透TRP超家族的成员。白藜芦醇(RESV)由于其药理特性而被广泛用于TRP通道调节,其中包括抗氧化剂和TRP抑制作用。RESV的保护功能和TRPV4对链脲佐菌素(STZ)诱导的小鼠神经性疼痛的贡献尚不清楚。这里,我们通过TRPV4对Ca2+内流的调节来评估RESV的影响,ROS介导的疼痛,凋亡,和小鼠背根神经节(DRGs)的氧化损伤。从32只老鼠中,四组诱导:对照组,RESV,STZ,和STZ+RESV。我们发现注射RESV减少了STZ诱导的TRPV4刺激引起的变化,进而增加了机械/热神经性疼痛,胞质Ca2+内流,TRPV4电流密度,氧化剂(脂质过氧化,线粒体ROS,和胞质ROS),和凋亡标志物(caspase-3、-8和-9)。RESV注射液还增加了STZ介导的DRG活力降低和谷胱甘肽的含量,谷胱甘肽过氧化物酶,维生素A,β-胡萝卜素,和大脑中的维生素E,红细胞,等离子体,肝脏,还有肾.所有这些研究结果表明,TRPV4刺激会产生氧化神经毒性,神经性疼痛,和STZ诱导的糖尿病小鼠的细胞凋亡。另一方面,由于通过RESV注射进行的TRPV4下调,神经毒性和细胞凋亡减少.
Diabetic peripheral neuropathy (DPN) is caused by several factors, including reactive free oxygen radicals (ROS)-induced excessive Ca2+ influx. Transient receptor potential (TRP) vanilloid 4 (TRPV4) is a member of the Ca2+-permeable TRP superfamily. Resveratrol (RESV) has been extensively utilized in TRP channel regulation due to its pharmacological properties, which include antioxidant and TRP inhibitory effects. The protective function of RESV and the contribution of TRPV4 to streptozotocin (STZ)-induced neuropathic pain in mice are still unclear. Here, we evaluated the effects of RESV through the modulation of TRPV4 on Ca2+ influx, ROS-mediated pain, apoptosis, and oxidative damage in the mouse dorsal root ganglion (DRGs). From the 32 mice, four groups were induced: control, RESV, STZ, and STZ + RESV. We found that the injection of RESV reduced the changes caused by the STZ-induced stimulation of TRPV4, which in turn increased mechanical/thermal neuropathic pain, cytosolic Ca2+ influx, TRPV4 current density, oxidants (lipid peroxidation, mitochondrial ROS, and cytosolic ROS), and apoptotic markers (caspase-3, -8, and -9). The RESV injection also increased the STZ-mediated reduction of viability of DRG and the amounts of glutathione, glutathione peroxidase, vitamin A, β-carotene, and vitamin E in the brain, erythrocytes, plasma, liver, and kidney. All of these findings suggest that TRPV4 stimulation generates oxidative neurotoxicity, neuropathic pain, and apoptosis in the STZ-induced diabetic mice. On the other hand, neurotoxicity and apoptosis were reduced due to the downregulation of TRPV4 carried out through the RESV injection.