本文選題：順鉑 + Ghrelin　； 參考：《青島大學(xué)》2017年碩士論文

【摘要】：目的:觀察順鉑對(duì)大鼠攝食、異食癖、體重、胃排空、胃運(yùn)動(dòng)及下丘腦、血漿ghrelin、orexin表達(dá)的影響。方法:雄性Wistar大鼠隨機(jī)分為低劑量順鉑處理組(3 mg/kg),高劑量順鉑處理組(6 mg/kg)和生理鹽水對(duì)照組,觀察大鼠攝食、攝入高嶺土量、體重及胃排空和胃運(yùn)動(dòng)的改變;Real-time PCR、ELISA法觀察順鉑對(duì)大鼠下丘腦、血漿ghrelin、orexin表達(dá)及攝食量的影響;19名接受順鉑經(jīng)導(dǎo)管動(dòng)脈灌注化療(TAI)的肝細(xì)胞患者(HCC),ELISA法檢測(cè)化療前和化療后血漿ghrelin、orexin的變化,用直觀類比標(biāo)度(VAS)(0-10)評(píng)估食欲和攝食量。結(jié)果:腹腔注射小劑量順鉑(3 mg/kg),大鼠攝食量與生理鹽水對(duì)照組相比無明顯改變。腹腔注射大劑量順鉑(6 mg/kg),大鼠24 h累計(jì)攝食量顯著少于生理鹽水對(duì)照組;與生理鹽水對(duì)照組相比,注射藥物后2-5 d,大鼠攝食量顯著降低。與生理鹽水組相比,腹腔注射小劑量順鉑(3 mg/kg)后,大鼠高嶺土攝入量無明顯改變。與生理鹽水組相比,腹腔注射大劑量順鉑(6 mg/kg),大鼠高嶺土攝入量降低。與生理鹽水組相比,腹腔注射小劑量順鉑(3 mg/kg)后,大鼠體重?zé)o明顯改變。與生理鹽水組相比,腹腔注射大劑量順鉑(6 mg/kg)后的第1天和第2天,大鼠體重降低,但差別無統(tǒng)計(jì)學(xué)意義,腹腔注射順鉑后的第3天到第5天,大鼠體重顯著降低。與生理鹽水組相比,腹腔注射小劑量順鉑(3 mg/kg),大鼠胃排空率無明顯差異。與生理鹽水組相比,腹腔注射順鉑大劑量順鉑(6 mg/kg),大鼠胃排空率降低。與生理鹽水組比,腹腔注射小劑量順鉑(3 mg/kg),大鼠胃收縮幅度無明顯改變。與生理鹽水組相比,腹腔注射順鉑大劑量順鉑(6mg/kg),大鼠胃收縮幅度降低。腹腔注射順鉑5天測(cè)量大鼠的胃收縮頻率。與生理鹽水組相比,腹腔注射小劑量順鉑(3 mg/kg),大鼠胃收縮頻率無顯著差異。與生理鹽水組相比,腹腔注射順鉑大劑量順鉑(6 mg/kg),大鼠胃收縮頻率降低。與生理鹽水組相比,大劑量順鉑(6 mg/kg)腹腔注射后的1-5d,血漿ghrelin濃度明顯降低。腹腔注射小劑量順鉑(3 mg/kg),1-4d時(shí)血漿ghrelin濃度顯著低于生理鹽水組,5d時(shí)血漿ghrelin濃度雖低于生理鹽水組,但無統(tǒng)計(jì)學(xué)意義。腹腔注射順鉑后1d-3d(3mg/kg或6mg/kg),與生理鹽水組相比,下丘腦ghreilin m RNA表達(dá)顯著降低,且呈顯著量效依賴關(guān)系,在第4d及第5d,與生理鹽水組相比,高劑量或低劑量順鉑均能夠抑制下丘腦ghreilin m RNA表達(dá),但兩種劑量相比無明顯差異。腹腔注射順鉑后1d起(3mg/kg或6mg/kg),與生理鹽水組相比,除第4d外其余時(shí)間點(diǎn),下丘腦orexin的mRNA表達(dá)量顯著減少,呈顯著量效依賴關(guān)系。在第4d只有高劑量組orexin的m RNA表達(dá)量顯著減少,而低劑量組orexin的m RNA表達(dá)量與生理鹽水組相比無統(tǒng)計(jì)學(xué)差異。與化療前相比,病人化療后1至8d的攝食量顯著降低,9 d后攝食量逐漸恢復(fù)。與化療前相比,患者化療后1、2d,病人食欲VASs顯著降低。在順鉑化療期間病人未發(fā)生嚴(yán)重不良反應(yīng)。與化療前相比,病人化療后的第1 d-3 d,血漿ghrelin水平顯著低于化療前�；熀蟮牡�4d,病人血漿ghrelin水平開始恢復(fù)。與順鉑化療前相比,化療后1~4d,病人血漿orexin濃度顯著降低,化療后的第5d,血漿orexin水平基本恢復(fù)到化療前水平。結(jié)論:順鉑可使大鼠攝食量減少,高嶺土的攝入量增加,體重降低,胃排空延遲,胃收縮頻率和幅度降低;順鉑可降低大鼠下丘腦和血漿ghrelin、orexin的m RNA表達(dá),HCC的TAI會(huì)降低血漿ghrelin、orexin水平,且患者攝食量明顯下降。
[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.
【學(xué)位授予單位】：青島大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R730.53

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 Grace Makari-Judson;Barry Braun;D Joseph Jerry;Wilson C Mertens;;Weight gain following breast cancer diagnosis: Implication and proposed mechanisms[J];World Journal of Clinical Oncology;2014年03期

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本文編號(hào)：1927850