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目的探讨5-羟色胺4(5-HT4)受体调节剂(激动剂和抑制剂)对肝部分切除(PH)后大鼠胃肠道5-羟色胺(5-HT)和肝再生的影响。方法 60只成年SD大鼠PH后分为对照组、西沙必利(激动剂)组和GR113808(抑制剂)组3组;西沙必利组PH后每12h按10mg/kg体重的西沙必利灌胃,GR113808组PH后每12h按3mg/kg体重的GR113808腹腔注射;分别于PH后0h、24h、48h、72h计算肝/体重比,并取血液、胃、小肠和肝组织;用免疫组织化学技术显示胃肠中5-HT免疫阳性(5-HTIR)细胞,用图像分析系统测定胃肠5-HTIR细胞平均灰度,用酶联免疫吸附法(ELESA)检测血液中的5-HT,用银染技术显示肝细胞核仁组织区相关嗜银蛋白(AgNORs)。结果与对照组比,1.西沙必利组胃肠中5-HTIR细胞数于PH后48～72h显著下降(P<0.05)、细胞的灰度于PH后24～72h显著上升(P<0.05),血中5-HT的含量于PH后24～72h显著上升(P<0.05),肝/体重比和肝组织AgNORs颗粒数在PH后48～72h显著增加(P<0.05);2.GR113808组在PH后24～72h期间,5-HTIR细胞数较对照组无显著性差异,但细胞的灰度显著下降(P<0.05或P<0.01),血中5-HT的含量显著下降(P<0.05或P<0.01),肝/体重比于48～72h显著下降(P<0.05或P<0.01),肝中AgNORs颗粒数于24～72h显著减少(P<0.05或P<0.01)。结论用5-HT4受体调节剂改变胃肠道5-HT的分泌量,可导致肝/体重比和肝细胞的转录活性发生相应的改变;胃肠道分泌的5-HT具有促进肝细胞增殖的作用。
Objective To investigate the effects of serotonin 4 (5-HT4) receptor modulators (agonists and inhibitors) on 5-hydroxytryptamine (5-HT) and liver regeneration in rats after partial hepatectomy (PH) Methods 60 adult SD rats were divided into 3 groups: control group, cisapride (agonist) group and GR113808 (inhibitor) group. After cisapride group PH was treated with 10 mg / kg body weight of cisapride The GR113808 group was injected intraperitoneally with GR113808 at a dose of 3mg / kg body weight every 12h after treatment with PH. The liver / body weight ratio was calculated at 0h, 24h, 48h, 72h after PH injection. Blood, stomach, small intestine and liver tissues were obtained by immunohistochemistry 5-HTIR cells in the gastrointestinal tract were displayed by technique. The average gray level of 5-HTIR cells in the gastrointestinal tract was measured by an image analysis system. 5-HT in the blood was detected by enzyme-linked immunosorbent assay (ELESA) Silver staining shows hepatocyte nucleolar organizer regions associated with AgNORs. Results Compared with the control group, the number of 5-HTIR cells in cisapride group decreased significantly at 48-72h after PH (P <0.05), and the gray value of cells increased significantly at 24-72h after PH (P <0.05) (P <0.05). The liver / body weight ratio and the number of AgNORs particles in liver increased significantly after 48-72h (P <0.05); 2. The expression of GR113808 There was no significant difference in the number of 5-HTIR cells between the 24th and 72th hours after PH treatment, but the gray scale of the cells was significantly decreased (P <0.05 or P <0.01) and the content of 5-HT in the blood was significantly decreased (P (P <0.05 or P <0.01). The liver / body weight ratio decreased significantly from 48 to 72 h (P <0.05 or P <0.01). The number of AgNORs particles in liver decreased significantly from 24 to 72 h (P <0.05 or P <0.01). Conclusion 5-HT4 receptor modulator can change the secretion of 5-HT in the gastrointestinal tract, resulting in a corresponding change of liver / body weight ratio and hepatocyte transcriptional activity. 5-HT secreted by the gastrointestinal tract can promote hepatocyte proliferation Role.