微生物来源的类胰酶可恢复外分泌性胰腺功能不全猪模型的生长并使脂质吸收正常化。

Pancreatic-like enzymes of microbial origin restore growth and normalize lipid absorption in a pig model with exocrine pancreatic insufficiency.

作者信息

Pierzynowska Kateryna, Valverde-Piedra Jose, Szymanczyk Sylwia, Prykhod'ko Olena, Pieszka Marek, Kardas Marek, Grochowska-Niedworok Elżbieta, Grabowski Tomasz, Winiarczyk Mateusz, Pierzynowski Stefan

机构信息

Department of Biology, Lund University, Lund, Sweden.

SGPlus, Malmo, Sweden.

出版信息

Arch Med Sci. 2018 Mar;14(2):407-414. doi: 10.5114/aoms.2018.73471. Epub 2018 Feb 21.

Abstract

INTRODUCTION

The standard therapy for exocrine pancreatic insufficiency (EPI) is porcine-derived pancreatic enzyme replacement therapy (PERT). In the present study we tested a new approach with a mixture of pancreatic-like enzymes of microbial origin (PLEM) in a 1-week efficacy study in EPI pigs. In addition to the conventionally used coefficient of fat and nitrogen absorption (CFA and CNA), parameters that more accurately reflect the nutritional and health status, such as changes in the lipemic index (LI), plasma triglyceride (TG) and non-esterified fatty acid (NEFA) levels, and somatic growth, were determined.

MATERIAL AND METHODS

A PLEM dose containing 120 000 active lipase units, 80 000 active protease units and 12 000 active amylase units (all from Sigma, St. Louis, MO) was given as a powder, twice daily with a meal (40 g fat/meal) to 8 EPI pigs for 7 days. Ten healthy pigs were used as a comparator.

RESULTS

The PLEM enhanced fat and protein digestion, and reversed growth impairment in EPI pigs. With treatment, CFA and CNA increased by 59% and 43% ( < 0.05), respectively. Although fat and protein absorption were lower than in the comparator, the postprandial blood lipid profile was normal as in healthy pigs. The mucosal thickness significantly increased by 27%, 50% and 26%, in the proximal, middle, and distal jejunum ( < 0.05) with treatment and resembled that of healthy animals.

CONCLUSIONS

Pancreatic-like enzymes of microbial origin supported somatic growth and normalized the postprandial lipid profile. As a measure of efficacy, postprandial LI, TG and NEFA are viable endpoints to be explored in human trials.

摘要

引言

外分泌性胰腺功能不全(EPI)的标准疗法是猪源性胰酶替代疗法(PERT)。在本研究中,我们在一项为期1周的EPI猪疗效研究中测试了一种使用微生物来源的类胰酶混合物(PLEM)的新方法。除了常规使用的脂肪和氮吸收系数(CFA和CNA)外,还测定了更准确反映营养和健康状况的参数,如血脂指数(LI)、血浆甘油三酯(TG)和非酯化脂肪酸(NEFA)水平的变化以及体细胞生长情况。

材料与方法

将含有120000活性脂肪酶单位、80000活性蛋白酶单位和12000活性淀粉酶单位(均来自密苏里州圣路易斯市的Sigma公司)的PLEM剂量制成粉末,每天两次与餐同服(每餐含40 g脂肪),给予8头EPI猪,持续7天。10头健康猪作为对照。

结果

PLEM增强了EPI猪的脂肪和蛋白质消化能力,并逆转了生长障碍。治疗后,CFA和CNA分别增加了59%和43%(P<0.05)。虽然脂肪和蛋白质吸收低于对照组,但餐后血脂谱与健康猪一样正常。治疗后,空肠近端、中段和远端的黏膜厚度分别显著增加了27%、50%和26%(P<0.05),与健康动物相似。

结论

微生物来源的类胰酶支持体细胞生长并使餐后血脂谱正常化。作为疗效指标,餐后LI、TG和NEFA是人体试验中值得探索的可行终点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f688/5868679/5ee5765ed62f/AMS-14-31799-g001.jpg

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