Vigna Steven R
Departments of Cell Biology and Medicine, Duke University Medical Center, Durham, NC 27710, USA.
V. A. Medical Center, Durham, NC 27705, USA.
Gastroenterol Res Pract. 2017;2017:8438172. doi: 10.1155/2017/8438172. Epub 2017 Apr 17.
toxin A is a colonic inflammatory agent that acts partially by activation of TRPV1 (transient receptor potential vanilloid type 1). Resiniferatoxin (RTX) is an excitotoxin that activates TRPV1 at low concentrations and defunctionalizes TRPV1 at high concentrations. RTX at various doses was injected intraluminally into isolated ileal segments in anesthetized rats. After 3 hours, the treated segments were removed and inflammation was assessed. This acute treatment with RTX resulted in biphasic responses: (1) an increase in inflammation similar to that caused by toxin A and capsaicin at low doses of up to 100 ng RTX and (2) no inflammatory effect of RTX at higher doses (1-100 g), consistent with a defunctionalizing or neurotoxic effect of RTX at high doses. Separately, anesthetized rats were treated with RTX enemas and one or four weeks later were challenged with toxin A. Toxin A-induced colitis was significantly inhibited one week after an RTX enema, and this effect was RTX dose dependent. When tested four weeks after administration of the RTX enema, protection against toxin A colitis was lost. In conclusion, an RTX enema protects against toxin A-induced colitis in rats for at least one week but less than four weeks.
毒素A是一种结肠炎症介质，其部分作用是通过激活TRPV1（瞬时受体电位香草酸亚型1）来实现的。树脂毒素（RTX）是一种兴奋性毒素，在低浓度时激活TRPV1，在高浓度时使TRPV1失活。将不同剂量的RTX经腔内注射到麻醉大鼠的离体回肠段中。3小时后，取出处理过的肠段并评估炎症情况。RTX的这种急性处理导致了双相反应：（1）在低剂量高达100 ng RTX时，炎症增加，类似于毒素A和辣椒素引起的炎症；（2）在较高剂量（1 - 100 μg）时，RTX没有炎症作用，这与RTX在高剂量时的失活或神经毒性作用一致。另外，给麻醉大鼠进行RTX灌肠，1周或4周后用毒素A进行攻击。RTX灌肠1周后，毒素A诱导的结肠炎受到显著抑制，且这种作用呈RTX剂量依赖性。当在RTX灌肠给药4周后进行测试时，对毒素A结肠炎的保护作用消失。总之，RTX灌肠可使大鼠免受毒素A诱导的结肠炎影响至少1周，但不到4周。
