侧脑室注射nesfatin-1抑制大鼠胃酸分泌

Nesfatin-1 suppresses gastric acid serection in rat

目的观察侧脑室注射nesfatin-1对大鼠胃黏膜泌酸功能的影响,并探讨其可能的作用机制。方法雄性SD大鼠,侧脑室置管后,每只大鼠分别给以侧脑室注射1、5和50 pmol的nesfatin-1及等体积的灭菌水(5μL/rat),于20 min及1、2、4和6 h处死大鼠,收集胃液,测定其胃酸的变化。并用RT-PCR、Western blot检测胃黏膜中组胺酸脱羧酶(HDC)mRNA及蛋白的表达,ELISA法检测胃体黏膜中组胺的含量。其后选择最强作用浓度进一步检测nes-fatin-1在不同作用时间点对大鼠胃酸分泌的影响。结果大鼠注射浓度为5和50 pmol的nesfatin-1后2 h,大鼠胃酸分泌减少,其中50 pmol作用最强(P<0.05)。同时大鼠胃黏膜中HDC mRNA及蛋白的表达受到抑制(P<0.05)。注射50 pmol的nesfatin-1在1,2 h能够抑制胃体黏膜中组胺的表达,2 h抑制更明显(P<0.05)。结论侧脑室注射nesfatin-1可呈剂量和时间依赖性的抑制大鼠胃酸的分泌,组胺信号通路可能参与了上述过程。

Objective To observe the effect of intracerebroventricular （ICV） injection of nesfatin-1 on gastric acid secretion in rats, meanwhile its possible mechanism is also been investigated. Methods Male Sprague-Dawley rats were selected, and after ICV cannula implanted, the rats were randomly divided into control group and nesfatin-1 group, and the nesfatin-1 group was injected intracerebroventricularly with different concentrations of nesfatin-1, control group was treated with the same amount of distilled water （5 μL/rat）. Optimum concentration of nesfatin-1 is used for the next subjects, then rats were sacrificed at different time points. The acid content of gastric juice were detected as before. The expression of histidine decarboxylase （HDC） mRNA and protein was examined by real- time PCR and Western blot. The changes in histamine in the gastric mucosa was detected by ELISA. Results ICV administration of nesfatin-1 significantly inhibited gastric acid output, the maximum inhibitory effect on gastric acid output was detected at the dose of 50 pmol/rat, and the optimum time for the gastric acid inhibition occured at 2 hours after ICV administration of nesfatin-1. Furthermore, nesfatin-1 decreased histidine decarboxylase （HDC） messenger RNA （mRNA） and protein expression levels in gastric mucosal tissue compaired to the control group. Conclusions Nesfatin-1 dose and time dependentlyinhibited gastric acid secretion by ICV injection in rat, the histamine signaling may be involved in this process.