Intestinal smooth muscle dysfunction develops postnatally in cystic fibrosis mice.
Intestinal smooth muscle dysfunction develops postnatally in cystic fibrosis mice.
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DOI：
10.1097/mpg.0b013e3182638bf4
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发表时间：
2012-12
影响因子：
2.9
通讯作者：
Mueller R
中科院分区：
文献类型：
--
作者：
De Lisle RC;Meldi L;Mueller R
肠蠕动障碍是囊性纤维化（CF）的影响之一，但何时及如何发展尚不清楚。本研究的目的是使用Cftr基因敲除小鼠来确定在发育过程中小肠圆形平滑肌何时发生功能障碍。野生型（WT）和CF型小鼠从出生后第5天（P5）到成年。小肠片被用来测量圆形肌肉的收缩活动。通过细菌16S基因的定量PCR检测细菌的过度生长。采用定量RT-PCR检测肠道基因表达。采用酶免疫法检测前列腺素E2 （PGE2）及其代谢产物。CF环肌对胆碱能刺激的反应在P5时与WT相似，在P7时有所受损，P14时严重受损。在CF肠中，细菌过度生长发生在P4，并维持到成年期。出生后不久，CF肠道中的类二十烷酸代谢基因表达与WT没有差异。磷脂酶A2基因、Pla2g4c和Pla2g5在CF小鼠P24时表达增加。前列腺素降解基因Hpgd和Ptgr1分别在P16和P24位点在CF中的表达低于WT。从7岁到成年，CF小鼠的PGE2水平显著升高。结果清楚地表明，CFTR缺乏本身并不会导致平滑肌功能障碍，因为P5 CF小鼠的圆形肌肉在P7-P14之间活动正常，功能障碍出现。
Intestinal dysmotility is one of the effects of cystic fibrosis (CF) but when and how this develops is not well understood. The goal of this study was to use the Cftr knockout mouse to determine when in development circular smooth muscle of the small intestine becomes dysfunctional. Wild type (WT) and CF mice were used at postnatal day 5 (P5) through adult. Pieces of small intestine were used to measure contractile activity of the circular muscle. Bacterial overgrowth was measured by quantitative PCR of the bacterial 16S gene. Intestinal gene expression was determined by quantitative RT-PCR. Prostaglandin E2 (PGE2) and its metabolites were measured by enzyme immunoassay. CF circular muscle response to cholinergic stimulation was similar to WT at P5, became somewhat impaired at P7, and was severely impaired by P14. In the CF intestine, bacterial overgrowth occurred by P4 and was maintained into adulthood. Eicosanoid metabolic gene expression in the CF intestine did not differ from WT shortly after birth. The phospholipase A2 genes, Pla2g4c and Pla2g5 exhibited increased expression in CF mice at P24. Prostaglandin degradative genes, Hpgd and Ptgr1, showed lower expression in CF as compared to WT at P16 and P24, respectively. PGE2 levels were significantly greater in CF mice at most ages from P7 through adulthood. The results clearly demonstrate that lack of CFTR itself does not cause smooth muscle dysfunction, as the circular muscle from P5 CF mice had normal activity and dysfunction developed between P7-P14.