| Objective:Motion sickness can be caused by a variety of motion environments (e.g., cars, boats, planes and space). The response, in terms of gastrointestinal and other peripheral changes, is characteristic of a general autonomic nervous disorder during motion sickness. However, studies on the motion sickness using common laboratory animals such as rats and mice are limited due to the lack of the ability to vomit. Therefore, it is essential to develop an animal model for motion sickness in rats and mice. The mechanism of motion sickness remains unclear. It has been demonstrated that motion sickness are influenced by both environmental and genetic factors. Swiprosin-1, a new adaptor protein, is a 240 amino-acid protein with predicted and molecular weights of 27 and 33 KDa. Our purpose is to optimize the evaluation of motion sickness, establish a novel animal model for motion sickness in rodents and investigate the role of swiprosin-1 in the pathogenesis of motion sickness.Methods:The evaluation criteria of the motion sickness which developed by our laboratory was optimized. The inherited mice sensitive or resistant to motion sickness were continued to culture. A group of 20 rats were subdivided into an experimental group and a control group. The rats of experimental group were treated with rotational stimulation for 40min. Then the level of ACTH, Gas, MTL, ET and INS in experimental group was measured by RIA and the biochemical indicator such as cholesterol total, carbamide, GPT, creatinine and triglyceride were measured by semi-automatic bioanalytical system. Immunohistochemistry analysis and immunofluorescent assay were used to examine the expression and function of swiprosin-1. The monolayer permeability of bEnd.3 cells was observed after treated with RNAi lentivirus targeting SWP gene.Results:1. The mice sensitive to motion sickness and the mice resistant to motion sickness were selected, copulated and cultivated respectively. The motion sickness index of the mice sensitivity to motion sickness is larger than 8 and the motion sickness index of the mice resistant to motion sickness is less than 2. After several generations of mice selected conditions, the susceptibility of sensitive to or resistant to motion sickness was increase gradually generation by generation. The motion sickness index between the mice sensitive to motion sickness and the mice resistant to motion sickness has shown significant difference. Now the thirteenth generation mice(F13), an inherited strain sensitive to and a strain resistant to motion sickness were obtained.2. The mice react to rotational stimulation during 8:00-12:00,12:00-16:00, 16:00-20:00 were observed. The motion sickness index during 12:00-16:00,16:00-20:00 are higher than 8:00-12:00 significantly. The results showed that we should fix a time by using this evaluation criteria. The most effective rotational stimulation is that stimulated in a rotator with alternately variable speed for 40min, rotated clockwise around a horizontal axis at an angular acceleration of 48°/s2 until the angular velocity reached 360°/s. Then the device was decelerated at an angular acceleration of 48°/s2 until rotation stopped. The piloerection, tremble, urinal and fecal incontinence in mice have no significant changed after treated with three different kinds of hypoxia, hot, and hypothermia.3. The rats of experimental groups were treated rotational stimulation with for 40min. There was no significant difference in the biochemical indicator and hormone level of rats.4. Swiprosin-1 was mainly distributed in endothelium cell and with high expression in bEnd.3 cells by immunohistochemistry. After treated with RNAi lentivirus targeting SWP gene, the monolayer permeability and the nitric oxide synthase of bEnd.3 cells were significant increased, and the level of IL-1 was no significant changed. The result showed that the low expression of swiprosin-1 may increase the monolayer permeability in bEnd.3 cells by increasing the activity of nitric oxide synthase.Compared with the mice resistant to motion sickness, the cerebral blood flow was much lower in the mice sensitive to motion sickness. The cerebral blood flow was significant increased after treated with RNAi lentivirus targeting SWP gene. It is suggested that the increase of cerebral blood flow might be important factors in inducing motion sickness.Conclusion:The motion sickness index is a sensitive indicator for motion sickness and can be used for evaluate the effects of anti-motion sickness new drugs. Swiprosin-1 distributed in endothelium cell and with high expression in bEnd.3 cells. Compared with the mice resistant to motion sickness, the cerebral blood flow was much lower in the mice sensitive to motion sickness. The cerebral blood flow significant increased after treated with RNAi lentivirus targeting SWP gene. The monolayer permeability and the nitric oxide synthase in bEnd.3 cells were increase by treated RNAi lentivirus targeting SWP gene. It is suggested that swiprosin-1 may play a role in motion sickness by increase cerebral capillary permeability.
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