动物模型 z-bo 2020-12-06 478

　　Introduction: The ideal patch must be adapted to the current needs of each patient in the current clinical situation. In order to provide a patch for most patients, various patch concepts continue to grow. For example, patch grids of various materials (prosthesis or biological origin), shapes (planar patches, plugs, and three-dimensional patches), light and heavy, and various coatings are available. With more and more data assessing the feasibility of new patches, the ultimate goal is to improve patient prognosis. Although clinical research is the best way to evaluate new patches, long-term evaluation of biocompatibility and strength still requires preclinical animal models. In particular, some important patch characteristics, such as inflammation, contraction, growth, remodeling, and adhesion formation of patches, can only be studied through experimental models, and patients can no longer evaluate these key factors. However, in order to compare and replicate them, it is important that different research groups use comparable research methods. However, in our past search for hernia models, we came across a variety of different models, resulting in almost no comparable hypotheses in published animal studies of hernia surgery. To support this hypothesis, we now conduct a systematic review of the literature on all animal models of hernia research between 2000 and 2014.

　　 Materials and methods: Literature search: Systematic literature search uses "EMBASE and PubMed. The search strategy is to find all the literature on abdominal wall hernia surgery models. Literature search was carried out with the help of experienced university librarians.

　　Research results: All parameters related to the studied animal model are scored in a standardized scoring table. All scoring parameters are mentioned in the supplementary data. First, the parameters of the animal model were evaluated, including subspecies. The article mentioned the sex, weight and age of the animals. In addition, a previously published model is used for scoring; this is defined as an explicit reference to the same animal model previously published. Details of the model used subsequently. This includes the size of the hernia defect and the size of the defect (where applicable), the location of the patch, and the size of the implanted patch.

　　 Results: A total of 315 articles were included in this study, including 168 research rats (53.3%), 66 research rabbits (21%), and 53 research pigs (16.8%). The remaining studies describe the use of mouse, guinea pig, primate, dog, goat, sheep and hamster models.

　　 Rat model: There are a total of 168 articles describing the use of the rat model, and a total of 9,150 rats were used in 164 studies. The remaining four studies did not determine the number of animals. The average number of animals used in each study was 56, with three groups of animals in each study. Most articles describe the use of SD (78 studies, 46.4%) or Wistar rats (78 studies, 46.4%). The subspecies were not defined in the two studies. In 85.1% of the studies, 66.7% used male rats, 16.7% females, and 1.8% used both sexes. In the remaining studies, gender was not defined (14.9%).

　　 Method: All rats underwent open patch implantation, and each animal received 1 (85.1%), 2 (13.1%), or 3 (0.6%) patches. Most models included the establishment of a real hernia defect model (121 articles, 72%), one study did not define a defect, and the rest (46 articles, 27.4%) did not cause a hernia defect. The defect size varies from 0.5 to 18 square centimeters, with an average of 4.2 square centimeters (median 4). Patches are placed in the bridging of defects (49 articles, 29.2%), intraperitoneal (40 articles, 23.8%), subcutaneous (30 articles, 17.9%), inlays (20 articles, 11.9%) or Preperitoneum (9 articles, 5.4%). The patch was cut into sizes, with a median value of 6 cm2 (average 5.76 cm2, range 0.8-20 cm2); the size of the patch was not defined in 29 articles (17.3%). The use of perioperative antibiotics to prevent infection was only mentioned in 7.1% of articles (12 studies). In these studies, the antibiotics used were penicillin, gentamicin, and fluoroquinolone antibiotics (4 studies). If animal models other than mice are added to the analysis, as many as 20.6% of articles describe the use of antibiotics, with cephalosporins used the most. In 15.5% of rat models, analgesics were used to relieve perioperative pain. In these 26 studies, opioid analgesics were used in most cases (17 articles, 10.1%), combined with non-steroidal anti-inflammatory drugs (2 articles, 1.2%), followed by NSAID (7 articles) , 4.2%) or topical analgesics (5 articles, 3%).

　　 Discussion: A critical review of the literature revealed the diversity of patch models; in the past ten years, many different models, animal species, patches, and parameters have been evaluated, making it difficult to compare with each other. The same model, including all parameters, has not been found to be implemented by different centers. In other words, all centers obviously use their own specific models. Due to the diversification of existing and new patch concepts, preclinical animal studies are necessary to evaluate the biocompatibility and effectiveness of new patches before clinical application. In addition, many important patches can only be properly studied using animal models. However, for experimental research to have an appropriate influence, the research published by different research groups needs to be comparable and reproducible. In this study, we tried to provide a systematic overview of patch studies in all available animal models. However, due to the large number of different animals used, we decided to focus on only one animal. Although large animal models like pigs are most similar to humans, more than 50% of experimental hernia studies have focused on rat models. Therefore, we decided to limit this overview and only elaborate on the rat model. This may be solved by a small animal model combining preliminary experiments and immunohistochemistry, which may be tested on a larger animal model, which is more like the anatomical structure of the human abdominal wall. The first problem to be solved is the use of most male rats. Although both male and female patients have incisional hernias, some clinical studies even report female sex as an independent risk factor, but almost all experimental studies only report the use of male rats. But one in seven authors did not report the sex of the animal, although there is more and more information about the effect of sex on the results. We believe that an important factor in choosing a hernia model should be that it is very similar to the human situation and follows the guidelines for human hernia repair. One difference between the human condition and most hernia models is the "hernia age". Most animal models described use acute hernia models, and defects are created during the patch placement process. A human hernia takes time to mature and may change the outcome after surgery. In order to further increase the impact of animal research on clinical practice, it may be good to translate hernia surgery guidelines into preclinical animal models. In order to further increase the impact of animal research on clinical practice, it may be good to translate hernia surgery guidelines into preclinical animal models.