| Objective: To observe the effect of cisplatin on plasma ghrelin,orexin expression in the hypothalamus and the influence of food intake.Method: The rats in the treatment group were treated with intraperitoneal injectio n of cisplatin(3 or 6 mg/kg),and the control group was given equal volume of normal saline.The food intake,kaolin consumptions,gastric emptying,amplitude and frequency of gastric motility,body wight of rats were measured.Real-time PCR and ELISA method to observe the effects of cisplatin on the food intake and ghrelin,orexin expression in hypothalamus and in plasma of rats;19 cisplatin transcatheter arterial infusion chemotherapy(TAI)of liver cells(HCC)patients,ELISA method to detect plasma ghrelin and orexin before and after chemotherapy,visual analog scale(VAS)(0 to 10)to evaluate appetite and food intake.Male Wistar rats were randomly divided into control group and cisplatin treatment group.Results: Compared with normal saline rats,intraperitoneal injection of small dose of cisplatin(3 mg/kg)showed no significant change in food intake(P > 0.05).Compared with normal saline rats,intraperitoneal injection of large dose of cisplatin(6 mg/kg),the cumulative intake of 24 h in rats was significantly reduced(P<0.05);Compared with normal saline rats,after the injection of 2-5d,the food intake of rats decreased significantly(P<0.05).Compared with normal saline rats,intraperitoneal injection of small dose of cisplatin(3 mg/kg)showed no significant change in Kaolin consumptions(P > 0.05).Compared with normal saline rats,intraperitoneal injection of large dose of cisplatin(6 mg/kg),the Kaolin consumptions of in rats was significantly reduced(P<0.05).Compared with normal saline rats,intraperitoneal injection of small dose of cisplatin(3 mg/kg)showed no significant change in body weight(P > 0.05).Compared with the normal saline group,high-dose intraperitoneal injection of cisplatin(6 mg/kg)after first days and second days,the body weight of rats decreased,but the difference was not statistically significant(P > 0.05).After the intraperitoneal injection of cisplatin 3 days to 5 days,the body weight of rats decreased significantly(P<0.05).Compared with the normal saline group,intraperitoneal injection of small dose of cisplatin(3 mg/kg),gastric emptying rate had no obvious difference(P > 0.05).Compared with normal saline group,intraperitoneal injection of high-dose cisplatin(6 mg/kg)significantly reduced the gastric emptying rate in rats(P<0.05).Compared with normal saline group,intraperitoneal injection of small dose of cisplatin(3 mg/kg)showed no significant changes in gastric contraction amplitude in rats(P > 0.05).Compared with normal saline group,intraperitoneal injection of high-dose cisplatin(6 mg/kg)reduced the gastric contraction amplitude in rats(P<0.05).The gastric contraction frequency was measured by intraperitoneal injection of cisplatin for 5 days.Compared with the saline group,there was no significant difference in gastric contraction frequency after rats injected intraperitoneally with small dose of cisplatin(3 mg/kg)(P > 0.05).Compared with normal saline group,intraperitoneal injection of cisplatin and high-dose cisplatin(6 mg/kg)reduced the gastric contraction frequency in rats(P<0.05).Compared with normal saline group,the plasma ghrelin concentration of was significantly reduced after intraperitoneal injection of large dose of cisplatin 1-5d(6 mg/kg)(P<0.05).Intraperitoneal injection of small dose of cisplatin(3 mg/kg),plasma ghrelin concentration was significantly lower than the normal saline group in1-4d(P<0.05).Plasma ghrelin concentration was lower than the normal saline group in 5d,but there was no statistical significant(P > 0.05).Compared with normal saline group,after intraperitoneal injection of cisplatin(3mg/kg or 6mg/kg)1-3d,ghrelin and m RN A expression in hypothalamus decreased significantly(P<0.05),and showed significant dose dependent relationship.Compared with normal saline group,after intraperitoneal injection of cisplatin(3mg/kg or 6mg/kg)4d and 5d,the high dose or low dose cisplatin can inhibit the expression of ghreilin and m RN A in hypothalamus.But there was no significant difference between the two doses(P > 0.05).Compared with normal saline group,After intraperitoneal injection of cisplatin,except for in 4d,the orexin expression of hypothalamus m RN A decreased significantly in the other time points(P<0.05),and showed a significant dose dependent relationship.The expression of m RNA was significantly decreased in the high dose group of orexin in 4d(P<0.05),while the expression of orexin in the low-dose group of m RN A was no significantly different from that in the saline group(P > 0.05).Compared with before chemotherapy,the food intake of patients was significantly decreased(P<0.05).and the food intake gradually recovered 9d after chemotherapy.Compared with before chemotherapy,the patient’s appetite was significantly decreased 1-2 d after chemotherapy(P<0.05).In the period of chemotherapy,patients without serious adverse reactions.Compared with pre chemotherapy,first 1d-3d,and plasma ghrelin levels in patients after chemotherapy were significantly lower than those before chemotherapy(P<0.05).After chemotherap y at 4D,the patient plasma ghrelin levels began to recover.Compared with cisplatin before chemotherapy,the concentration of orexin in plasma of patients decreased significantly after chemotherapy 1 to 4d,and the level of plasma orexin was basically return to the level of chemotherapy before 5d(P<0.05).Conclusion: C isplatin can decrease the food intake,body weight,gastric emptying,amplitude and frequency of gastric motility,and increase kaolin kaolin consumptions in rats.C isplatin can reduce rat hypothalamus and plasma ghrelin and orexin mRNAexpression,HCC TAI lowers plasma acylation ghrelin,orexin,and food intake. |
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