Measurements of rat and mouse gastrointestinal pH fluid and lymphoid tissue, and implications for in-vivo experiments
Measurements of rat and mouse gastrointestinal pH fluid and lymphoid tissue, and implications for in-vivo experiments
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DOI：
10.1211/jpp.60.1.0008
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发表时间：
2008-01-01
影响因子：
3.3
通讯作者：
Murdan, Suclaxshina
中科院分区：
文献类型：
--
作者：
McConnell, Emma L.;Basit, Abdul W.;Murdan, Suclaxshina
为了在口服药物和疫苗递送的体内研究中有效地使用啮齿动物模型，必须了解胃肠道中的条件。一些基本信息目前不可用或不完整。我们已经研究了pH值、水含量和淋巴组织分布沿着胃肠道以及胃体积，因为这些对于我们研究pH响应性药物递送和结肠疫苗接种至关重要。将观察到的值与人类中的值进行比较，以指示啮齿动物模型的有效性。小鼠胃pH值为3.0（进食）和4.0（禁食），大鼠相应值为3.2（进食）和3.9（禁食）。平均肠道pH值低于人类（小鼠< pH 5.2;大鼠< pH 6.6）。这使人们对啮齿动物在针对大肠/远端肠道的肠溶药物载体研究中的使用产生了疑问。进食和禁食小鼠的胃肠道含水量分别为0.98 +/- 0.4和0.81 +/- 1.3 mL，进食和禁食大鼠的胃肠道含水量分别为7.8 +/- 1.5和3.2 +/- 1.8 mL。当体重标准化时，小鼠和大鼠胃肠道中每kg体重的水含量高于人。小鼠和大鼠的胃容量分别约为0.4 mL和3.4 mL。低液体体积和胃容量对这些动物模型中固体剂型的测试具有影响。在大鼠和小鼠结肠中测量了大量类似于小肠派尔集合淋巴结的淋巴组织，显示了结肠接种的可行性，这一途径可能被证明与更常用的口服疫苗具有不同的应用。在小鼠和大鼠盲肠中也有淋巴组织存在的报道。
To use rodent models effectively in in-vivo investigations on oral drug and vaccine delivery, the conditions in the gastrointestinal tract must be understood. Some fundamental information is currently unavailable or incomplete. We have investigated the pH, water content and lymphoid tissue distribution along the gastrointestinal tract, as well as the stomach volume, as these were critical to our investigations on pH-responsive drug delivery and colonic vaccination. The observed values were compared with those in man as an indication of the validity of the rodent model. The mouse stomach pH was 3.0 (fed) and 4.0 (fasted), and the corresponding values in the rat were 3.2 (fed) and 3.9 (fasted). The mean intestinal pH was lower than that in man (< pH 5.2 in the mouse; < pH 6.6 in the rat). This brings into question the use of rodents in investigations on enteric-coated drug carriers targeted to the large intestine/distal gut. The water content in the gastrointestinal tract in the fed and fasted mouse was 0.98 +/- 0.4 and 0.81 +/- 1.3 mL, respectively, and in the fed and fasted rat was 7.8 +/- 1.5 and 3.2 +/- 1.8 mL. When normalized for body weight, there was more water per kg body weight in the gastrointestinal tracts of the mouse and rat, than in man. The stomach capacity was found to be approximately 0.4 and 3.4 mL for mice and rats, respectively. The low fluid volume and stomach capacity have implications for the testing of solid dosage forms in these animal models. Substantial amounts of lymphoid tissue analagous to small intestinal Peyer's patches were measured in the rat and mouse colon, showing the feasibility of colonic vaccination, a route which might prove to have different applications to the more commonly studied oral vaccines. The existence of lymphoid tissue in the mouse and rat caecum has also been reported.