Jaworek Jolanta, Bonior Joanna, Pierzchalski Piotr, Tomaszewska Romana, Stachura Jerzy, Sendur Ryszard, Leja Anna, Jachimczak Bozena, Konturek Peter C, Bielański Władysław, Pawlik Wiesław, Konturek Stanisław J
Department of Physiology, Jagiellonian University Medical College, Cracow, Poland.
Pancreatology. 2002;2(2):89-99. doi: 10.1159/000055897.
Recent identification of specific leptin receptors in the pancreas suggests that this peptide may also play some role in this gland.
To examine the effect of intraperitoneal (i.p.) or intracerebroventricular (i.c.v.) administration of leptin in rats on caerulein-induced pancreatitis (CIP), pancreatic gene expression of leptin and inflammatory cytokine production.
Caerulein (25 micrograms/kg) was infused subcutaneously into conscious rats over 5 h to produce CIP. Leptin (1, 5, or 10 micrograms/kg) was injected i.p. or i.c.v. 30 min prior to the CIP induction. The plasma level of TNF alpha and IL-4 was determined by ELISA, while plasma leptin was measured by RIA and leptin gene expression in pancreas by RT-PCR.
CIP was characterized by the usual pancreatic edema, reduction in pancreatic blood flow (PBF) and an increase in serum levels of amylase, TNF alpha and IL-4. Pretreatment with i.p. or i.c.v. leptin of the CIP rats partially reversed the harmful effects of CIP on the pancreas, and reduced pancreatic inflammation and the fall in PBF. This was accompanied by a dose-dependent reduction in serum levels of amylase and TNF alpha, while serum IL-4 in the CIP rats pretreated with leptin rose dose-dependently as compared to control rats with CIP alone. Pretreatment with leptin resulted in the dose-dependent rise in plasma leptin level over that observed in vehicle-treated controls. Leptin mRNA expression in the pancreas was dose-dependently increased after infusion of caerulein. Leptin content in isolated pancreatic acini was also increased dose-dependently by caerulein added to the incubation medium bathing these acini.
(1) Exogenous leptin protects the pancreas against damage by CIP; (2) endogenous leptin seems to limit the extend of pancreatic damage, and (3) these protective effects of leptin could be attributed to the reduction in TNF alpha and to the increase in IL-4 production.
最近在胰腺中发现了特定的瘦素受体，这表明该肽可能在这个腺体中也发挥着某种作用。
研究腹腔内（i.p.）或脑室内（i.c.v.）给予大鼠瘦素对雨蛙肽诱导的胰腺炎（CIP）、胰腺瘦素基因表达及炎性细胞因子产生的影响。
将雨蛙肽（25微克/千克）在5小时内皮下注入清醒大鼠以诱导CIP。在诱导CIP前30分钟腹腔内或脑室内注射瘦素（1、5或10微克/千克）。通过酶联免疫吸附测定法（ELISA）测定血浆肿瘤坏死因子α（TNFα）和白细胞介素4（IL-4）水平，通过放射免疫分析法（RIA）测定血浆瘦素水平，并通过逆转录聚合酶链反应（RT-PCR）测定胰腺中瘦素基因表达。
CIP的特征为常见的胰腺水肿、胰腺血流（PBF）减少以及血清淀粉酶、TNFα和IL-4水平升高。CIP大鼠腹腔内或脑室内注射瘦素预处理可部分逆转CIP对胰腺的有害影响，减轻胰腺炎症及PBF下降。这伴随着血清淀粉酶和TNFα水平的剂量依赖性降低，而与仅患有CIP的对照大鼠相比，用瘦素预处理的CIP大鼠血清IL-4呈剂量依赖性升高。与用赋形剂处理的对照相比，瘦素预处理导致血浆瘦素水平呈剂量依赖性升高。注入雨蛙肽后，胰腺中瘦素mRNA表达呈剂量依赖性增加。添加到培养这些腺泡的孵育培养基中的雨蛙肽也使分离的胰腺腺泡中的瘦素含量呈剂量依赖性增加。
（1）外源性瘦素可保护胰腺免受CIP损伤；（2）内源性瘦素似乎可限制胰腺损伤程度；（3）瘦素的这些保护作用可能归因于TNFα的减少和IL-4产生的增加。
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