Ghrelin在重症急性胰腺炎并发肾损伤中的作用

Roles of Ghrelin in Severe Acute Pancreatitis Associated with Kidney Injury

目的探讨Ghrelin在重症急性胰腺炎(SAP)并肾损伤中的作用以及外源性褪黑素对其的影响。方法 72只大鼠随机分为对照组(C组,n=24)、SAP组(A组,n=24)和褪黑素干预组(M组,n=24)。A组分3次腹腔内注射6%L-精氨酸(L-Arg)1.5g·kg-1·次-1建立SAP模型;C组同法注射等量生理盐水;M组于首次注射L-Arg前0.5h腹腔内注射1%褪黑素50μg/kg。各实验组大鼠于末次腹腔内注射后6h、12h和24h分批处死。光镜下对胰腺和肾组织进行病理学评分,用血清淀粉酶试剂盒测定血清淀粉酶,用ELISA检测血清IL-6,应用RT-PCR检测肾脏Ghrelin及NF-κB p65mRNA表达。结果 A组各时点胰腺及肾脏病理评分、血清淀粉酶及IL-6、肾脏NF-κB p65mRNA表达均较C组显著升高(P<0.05),而同时点Ghrelin mRNA表达较C组明显降低(P<0.05);M组各时点胰腺及肾脏病理评分、血清淀粉酶及IL-6、肾脏NF-κB p65mRNA表达均较A组显著降低(P<0.05),而同时点Ghrelin mRNA表达较A组升高(P<0.05)。结论 Ghrelin在急性胰腺炎并肾损伤时的表达可能与病变严重程度有关。外源性褪黑素可能通过抑制NF-κB p65的表达而减轻急性胰腺炎并肾损伤,并可能使Ghrelin在肾脏中表达增多。

Objective To investigate the roles of Ghrelin in acute necrotizing pancreatitis（SAP）associated with kidney injury in rats,and assess the effect of ectogenic melatonin on Ghrelin activity.Methods Seventy-two SD rats were randomly divided into control group（group C,n=24）,SAP group（group A,n=24）and melatonin intervention group（group M,n=24）.In group A,the rats were injected intraperitoneally three times with 6%L-arginine（1.5 g/kg） in an interval of 1 hour for SAP.In group C,the rats received the same amount of saline at the same time.In group M,1%melatonin（50μg/kg）was administered intraperitoneally 0.5 hour before L-arginine injection.The rats were killed at 6 hours,12 hours and 24 hours after the last intraperitoneal injection.The pathologic changes of pancreas and kidney were observed and graded under microscope.The level of serum amylase was detected.The level of serum IL-6 was determined by ELISA and the expression of Ghrelin mRNA and NF-κB p65 mRNA in kidney were evaluated by RT-PCR.Results The pathologic scores of the pancreas and kidney,the level of serum-amylase and IL-6 in serum,the expression of NF-κB p65 mRNA in kidney of group A were significantly higher than those of group C（P〈0.05）,while the expression of Ghrelin mRNA in kidney of group A was lower than that of group C（P〈0.05）.The pathologic scores of the pancreas and kidney,the levels of serum amylase and IL-6,the expression of NF-κB p65 mRNA in kidney of group M were significantly lower than those of group A（P〈0.05）,while the expression of Ghrelin mRNA in kidney of group A was higher than that of group A（P〈0.05）.Conclusion The expression of Ghrelin may concerned with the level of kidney injury in acute pancreatitis.Ectogenic melatonin may alleviate kidney injury by its inhibition of NF-κB p65 in acute pancreatitis,and may increase the expression of Ghrelin in kidney.