Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, Shandong, China.
Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, Shandong, China.
Neuropeptides. 2017 Dec;66:69-80. doi: 10.1016/j.npep.2017.09.003. Epub 2017 Sep 28.
To investigate ghrelin projection from the lateral hypothalamus area (LHA) to the dorsal vagal complex (DVC) and its regulation of gastric motility in cisplatin-treated rats.
In the present study, the protein and mRNA expression of ghrelin and its receptor GHSR-1a were measured by Western blot and PCR, respectively. The ghrelin fiber projections arising from the LHA and projecting to the DVC were investigated by retrograde tracing combined with fluoro-immunohistochemical staining. The effects of ghrelin in the DVC, electrical stimulation of the LHA, and electrical lesion of the DVC on gastric motility were measured in cisplatin-treated rats.
Ghrelin fibers originating in the LHA projected to the DVC. The protein and mRNA expression of GHSR-1a was greater in cisplatin-treated rats than in saline-treated rats. Conversely, the expression of ghrelin in the LHA and DVC was reduced in cisplatin-treated rats. Cisplatin treatment also reduced gastric contractions. Ghrelin administrated into the DVC significantly promoted gastric motility, an effect completely blocked by treatment with the ghrelin receptor antagonist [D-Lys-3]-GHRP-6. In addition, electrical stimulation of the LHA promoted gastric motility, though this effect was much weaker in cisplatin-treated rats than in control rats. The excitatory effect of electrical stimulation of the LHA on gastric motility was partially blocked by pretreatment of the DVC with [D-Lys-3]-GHRP-6. Electrical lesion of the DVC diminished the excitatory effect that was induced by electrical stimulation of the LHA.
DVC, especially AP, may have a role for gastric contraction induced by the stimulation of the LHA. This regulation on gastric motility was weaker in cisplatin-treated rats than in saline-treated rats, possibly due to reduced ghrelin expression in the LHA and ghrelin projection from the LHA to the DVC.
探讨外侧下丘脑区（LHA）向迷走神经背核（DVC）投射的生长激素释放肽（ghrelin）及其对顺铂处理大鼠胃动力的调节作用。
本研究通过 Western blot 和 PCR 分别测量 ghrelin 和其受体 GHSR-1a 的蛋白和 mRNA 表达。通过逆行示踪结合荧光免疫组织化学染色研究 LHA 起源的 ghrelin 纤维投射到 DVC。在顺铂处理的大鼠中测量 DVC 中的 ghrelin、LHA 的电刺激和 DVC 的电损伤对胃动力的影响。
起源于 LHA 的 ghrelin 纤维投射到 DVC。与生理盐水处理的大鼠相比，顺铂处理的大鼠中 GHSR-1a 的蛋白和 mRNA 表达增加。相反，LHA 和 DVC 中的 ghrelin 表达在顺铂处理的大鼠中减少。顺铂处理还降低了胃收缩。DVC 中给予 ghrelin 显著促进胃动力，该作用被 ghrelin 受体拮抗剂[D-Lys-3]-GHRP-6 完全阻断。此外，LHA 的电刺激促进胃动力，但在顺铂处理的大鼠中作用比在对照大鼠中弱。DVC 中的 [D-Lys-3]-GHRP-6 预处理部分阻断了 LHA 电刺激对胃动力的兴奋作用。DVC 的电损伤减弱了 LHA 电刺激引起的兴奋作用。
DVC，特别是 AP，可能在 LHA 刺激引起的胃收缩中起作用。这种对胃动力的调节作用在顺铂处理的大鼠中比在生理盐水处理的大鼠中较弱，可能是由于 LHA 中 ghrelin 表达减少和 LHA 向 DVC 的 ghrelin 投射减少所致。
