顺铂对大鼠摄食、胃动力及Ghrelin和Orexin表达的影响

发布时间：2018-05-24 05:28

本文选题：顺铂 + Ghrelin　；参考：《青岛大学》2017年硕士论文

【摘要】：目的:观察顺铂对大鼠摄食、异食癖、体重、胃排空、胃运动及下丘脑、血浆ghrelin、orexin表达的影响。方法:雄性Wistar大鼠随机分为低剂量顺铂处理组(3 mg/kg),高剂量顺铂处理组(6 mg/kg)和生理盐水对照组,观察大鼠摄食、摄入高岭土量、体重及胃排空和胃运动的改变;Real-time PCR、ELISA法观察顺铂对大鼠下丘脑、血浆ghrelin、orexin表达及摄食量的影响;19名接受顺铂经导管动脉灌注化疗(TAI)的肝细胞患者(HCC),ELISA法检测化疗前和化疗后血浆ghrelin、orexin的变化,用直观类比标度(VAS)(0-10)评估食欲和摄食量。结果:腹腔注射小剂量顺铂(3 mg/kg),大鼠摄食量与生理盐水对照组相比无明显改变。腹腔注射大剂量顺铂(6 mg/kg),大鼠24 h累计摄食量显著少于生理盐水对照组;与生理盐水对照组相比,注射药物后2-5 d,大鼠摄食量显著降低。与生理盐水组相比,腹腔注射小剂量顺铂(3 mg/kg)后,大鼠高岭土摄入量无明显改变。与生理盐水组相比,腹腔注射大剂量顺铂(6 mg/kg),大鼠高岭土摄入量降低。与生理盐水组相比,腹腔注射小剂量顺铂(3 mg/kg)后,大鼠体重无明显改变。与生理盐水组相比,腹腔注射大剂量顺铂(6 mg/kg)后的第1天和第2天,大鼠体重降低,但差别无统计学意义,腹腔注射顺铂后的第3天到第5天,大鼠体重显著降低。与生理盐水组相比,腹腔注射小剂量顺铂(3 mg/kg),大鼠胃排空率无明显差异。与生理盐水组相比,腹腔注射顺铂大剂量顺铂(6 mg/kg),大鼠胃排空率降低。与生理盐水组比,腹腔注射小剂量顺铂(3 mg/kg),大鼠胃收缩幅度无明显改变。与生理盐水组相比,腹腔注射顺铂大剂量顺铂(6mg/kg),大鼠胃收缩幅度降低。腹腔注射顺铂5天测量大鼠的胃收缩频率。与生理盐水组相比,腹腔注射小剂量顺铂(3 mg/kg),大鼠胃收缩频率无显著差异。与生理盐水组相比,腹腔注射顺铂大剂量顺铂(6 mg/kg),大鼠胃收缩频率降低。与生理盐水组相比,大剂量顺铂(6 mg/kg)腹腔注射后的1-5d,血浆ghrelin浓度明显降低。腹腔注射小剂量顺铂(3 mg/kg),1-4d时血浆ghrelin浓度显著低于生理盐水组,5d时血浆ghrelin浓度虽低于生理盐水组,但无统计学意义。腹腔注射顺铂后1d-3d(3mg/kg或6mg/kg),与生理盐水组相比,下丘脑ghreilin m RNA表达显著降低,且呈显著量效依赖关系,在第4d及第5d,与生理盐水组相比,高剂量或低剂量顺铂均能够抑制下丘脑ghreilin m RNA表达,但两种剂量相比无明显差异。腹腔注射顺铂后1d起(3mg/kg或6mg/kg),与生理盐水组相比,除第4d外其余时间点,下丘脑orexin的mRNA表达量显著减少,呈显著量效依赖关系。在第4d只有高剂量组orexin的m RNA表达量显著减少,而低剂量组orexin的m RNA表达量与生理盐水组相比无统计学差异。与化疗前相比,病人化疗后1至8d的摄食量显著降低,9 d后摄食量逐渐恢复。与化疗前相比,患者化疗后1、2d,病人食欲VASs显著降低。在顺铂化疗期间病人未发生严重不良反应。与化疗前相比,病人化疗后的第1 d-3 d,血浆ghrelin水平显著低于化疗前。化疗后的第4d,病人血浆ghrelin水平开始恢复。与顺铂化疗前相比,化疗后1~4d,病人血浆orexin浓度显著降低,化疗后的第5d,血浆orexin水平基本恢复到化疗前水平。结论:顺铂可使大鼠摄食量减少,高岭土的摄入量增加,体重降低,胃排空延迟,胃收缩频率和幅度降低;顺铂可降低大鼠下丘脑和血浆ghrelin、orexin的m RNA表达,HCC的TAI会降低血浆ghrelin、orexin水平,且患者摄食量明显下降。
[Abstract]:Objective: To observe the effect of cisplatin on feeding, fevy, body weight, gastric emptying, gastric motility and hypothalamus, and the expression of ghrelin and orexin in plasma. Methods: male Wistar rats were randomly divided into low dose cisplatin treatment group (3 mg/kg), high dose cisplatin treatment group (6 mg/kg) and normal saline control group, to observe the feeding of rats, the amount of kaolin, weight and stomach. Changes in emptying and gastric motility; the effects of cisplatin on hypothalamus, ghrelin, orexin expression and intake of plasma in rats with Real-time PCR and ELISA; 19 hepatocyte patients (HCC) receiving cisplatin via catheter artery perfusion chemotherapy (TAI). The ELISA method was used to detect the changes of ghrelin and orexin in plasma before and after chemotherapy, with a visual analogical scale (VAS) (0-10). Results: a small dose of cisplatin (3 mg/kg) had no significant changes in the intake of cisplatin (6 mg/kg), and the total intake of 24 h in rats was significantly less than that in the normal saline control group. Compared with the physiological saline control group, the diet was 2-5 d after the injection of the drug, and the intake of the rats was significant. Compared with the saline group, the intake of kaolin in rats was not significantly changed after intraperitoneal injection of small dose cisplatin (3 mg/kg). Compared with the saline group, a large dose of cisplatin (6 mg/kg) was injected into the abdominal cavity and the intake of kaolin in rats was reduced. The body weight of rats was not significantly changed after intraperitoneal injection of small dose of cisplatin (3 mg/kg). Compared with the saline group, the weight of rats was reduced in first days and second days after intraperitoneal injection of high dose cisplatin (6 mg/kg), but the difference was not statistically significant. The weight of rats decreased significantly from third days to fifth days after cisplatin intraperitoneal injection. Compared with the saline group, the abdominal injection of small dose of cisplatin (3 mg/kg) had no significant difference between the rats' gastric emptying rate. Compared with the saline group, the gastric emptying rate of rats was reduced by intraperitoneal injection of cisplatin with cisplatin (6 mg/kg). Compared with the normal saline group, the abdominal injection of small dose of cisplatin (3 mg/kg) was not significantly changed. Compared with the saline group, the intraperitoneal injection of cisplatin large dose Liang Shunbo (6mg/kg), the gastric contraction amplitude of rats was reduced. Cisplatin was injected intraperitoneally. The gastric contraction frequency of rats was measured on the 5 day. Compared with the saline group, there was no significant difference in the gastric contraction frequency of rats by intraperitoneal injection of small dose of cisplatin (3 mg/kg). Compared with the normal saline group, the abdominal injection of cisplatin (6 mg/kg) and a large dose of cisplatin (6 mg/kg) decreased the gastric contraction frequency. Compared with the saline group, the high dose cisplatin (6 mg/kg) after intraperitoneal injection of cisplatin was compared with the saline group. 5D, plasma concentration of ghrelin was significantly reduced. Intraperitoneal injection of small dose cisplatin (3 mg/kg), 1-4d plasma ghrelin concentration was significantly lower than the normal saline group, 5D plasma ghrelin concentration was lower than the normal saline group, but no statistical significance. 1d-3d (3mg/kg or 6mg/kg) after intraperitoneal injection of cisplatin (3mg/kg or 6mg/kg), compared with the saline group, ghreilin m to express the hypothalamus. Compared with the normal saline group, high or low dose cisplatin inhibited the ghreilin m RNA expression in the hypothalamus compared to the saline group at 4D and 5D, but there was no significant difference between the two doses. 1D (3mg/kg or 6mg/kg) after intraperitoneal injection of cisplatin (3mg/kg or 6mg/kg), compared with the normal saline group, the hypothalamus or was in addition to the rest of the other time points. The expression of mRNA in Exin was significantly reduced and showed a significant dose effect dependence. The m RNA expression of orexin in the high dose group was significantly reduced in 4D, while the m RNA expression of orexin in the low dose group was not significantly different from that in the saline group. Compared with the chemotherapy before chemotherapy, the intake of 1 to 8D after chemotherapy decreased significantly, and the feeding volume gradually recovered after 9 d. Compared with chemotherapy before chemotherapy, the patient's appetite for 1,2d decreased significantly after chemotherapy. There was no serious adverse reaction in patients with cisplatin chemotherapy. Compared with pre chemotherapy, first D-3 d after chemotherapy, plasma ghrelin level was significantly lower than before chemotherapy. 4D after chemotherapy, the patient's plasma ghrelin level began to recover. Compared with cisplatin chemotherapy, chemotherapy was compared. After 1~4d, the plasma concentration of orexin decreased significantly, and the level of plasma orexin after chemotherapy was basically restored to pre chemotherapy level. Conclusion: Cisplatin can reduce the intake of diet, increase the intake of kaolin, decrease the body weight, delay the gastric emptying, decrease the frequency and amplitude of gastric contraction, and decrease the m in the hypothalamus and plasma of rats, and the m of the plasma ghrelin and orexin. RNA expression, HCC TAI decreased plasma ghrelin and orexin levels, and the intake of food decreased significantly.
【学位授予单位】：青岛大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R730.53

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