Higham A, Vaillant C, Yegen B, Thompson D G, Dockray G J
Physiological Laboratory, University of Liverpool.
Gut. 1997 Jul;41(1):24-32. doi: 10.1136/gut.41.1.24.
Antral motility and the hormone cholecystokinin (CCK) are major determinants of the rate of gastric emptying. The relation between CCK and antral neurons in regulating gastric emptying is uncertain. Benzalkonium chloride (BAC) causes selective lesions in gut myenteric neurons after serosal application.
To develop a model of antral denervation using BAC to enable the study of the relation between CCK and antral neurons in regulating gastric emptying.
BAC, vehicle or the afferent neurotoxin capsaicin were applied to the serosal surface of the rat antrum or corpus; neurochemical markers of intrinsic and afferent neurons were detected by using immunohistochemistry and radioimmunoassay. Gastric retention of solids was determined after fasting, and emptying of liquids was measured in rats with gastric fistulae.
In BAC treated rats radioimmunoassay of tissue extracts revealed a dose related specific loss of gastrin releasing peptide, substance P, and vasoactive intestinal polypeptide immunoreactivities from the treated region, and immunohistochemistry revealed loss of the neuronal marker PGP 9.5 and the afferent neuropeptide calcitonin gene related peptide (CGRP). Adjacent untreated regions were unaffected by BAC, with the exception that CGRP was depleted in both corpus and antrum after antral treatment. After antral BAC treatment fasted rats retained solids for over 48 hours. Moreover, in antrally denervated rats with gastric fistulae, the emptying of saline, acid and peptone was delayed substantially. The CCK dependent inhibition of gastric emptying of peptone was preserved after antral treatment with BAC.
Serosal BAC causes lesions in the innervation of the treated region of the stomach. The innervation of the antrum is essential for normal emptying of both liquids and solids, but the inhibition of gastric emptying produced by CCK is not dependent on antral neurons.
胃窦运动和胆囊收缩素（CCK）是胃排空速率的主要决定因素。CCK与胃窦神经元在调节胃排空过程中的关系尚不确定。苯扎氯铵（BAC）经浆膜应用后可导致肠道肌间神经元发生选择性损伤。
利用BAC建立胃窦去神经支配模型，以研究CCK与胃窦神经元在调节胃排空过程中的关系。
将BAC、赋形剂或传入神经毒素辣椒素应用于大鼠胃窦或胃体的浆膜表面；采用免疫组织化学和放射免疫分析法检测内在神经元和传入神经元的神经化学标志物。禁食后测定固体食物在胃内的潴留情况，并在有胃瘘的大鼠中测量液体排空情况。
在BAC处理的大鼠中，对组织提取物进行放射免疫分析发现，处理区域胃泌素释放肽、P物质和血管活性肠多肽免疫反应性呈剂量依赖性特异性丧失，免疫组织化学显示神经元标志物PGP 9.5和传入神经肽降钙素基因相关肽（CGRP）丧失。相邻未处理区域未受BAC影响，但胃窦处理后胃体和胃窦中的CGRP均减少。胃窦BAC处理后，禁食大鼠的固体食物潴留超过48小时。此外，在有胃瘘的胃窦去神经支配大鼠中，盐水、酸和蛋白胨的排空显著延迟。BAC胃窦处理后，CCK对蛋白胨胃排空的抑制作用得以保留。
浆膜下BAC可导致胃处理区域的神经支配损伤。胃窦神经支配对于液体和固体的正常排空至关重要，但CCK对胃排空的抑制作用不依赖于胃窦神经元。
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