ObjectiveTo explore the feasibility of establishment of a artificial joint aseptic loosening mouse model by cobalt-chromium particles stimulation.MethodsTwenty-four 8-week-old male severe combined immunodeficient (SCID) mice were divided into experimental group (n=12) and control group (n=12). The titanium nail was inserted into the tibial medullary cavity of mouse in the two groups to simulate artificial joint prosthesis replacement. And the cobalt-chromium particles were injected into the tibial medullary cavity of mouse in experimental group. The survival of the mouse was observed after operation; the position of the titanium nail and the bone mineral density of proximal femur were observed by X-ray film, CT, and Micro-CT bone scanning; and the degree of dissolution of the bone tissue around the tibia was detected by biomechanical test and histological staining.ResultsTwo mice in experimental group died, and the rest of the mice survived until the experiment was completed. Postoperative imaging examination showed that there was no obvious displacement of titanium nails in control group, and there were new callus around the titanium nails. In experimental group, there was obvious osteolysis around the titanium nails. The bone mineral density of the proximal tibia was 91.25%±0.67%, and the maximum shear force at the tibial nail-bone interface was (5.93±0.85) N in experimental group, which were significantly lower than those in control group [102.07%±1.87% and (16.76±3.09) N] (t=5.462, P=0.041; t=3.760, P=0.046). Histological observation showed that a large number of inflammatory cells could be seen around the titanium nails in experimental group, while there was no inflammatory cells, and obvious bone tissue formation was observed in control group.ConclusionThe artificial joint aseptic loosening mouse model can be successfully established by cobalt-chromium particles stimulation.
Objective To establish a modeling method for an animal model simulating the decline of digestive function after a large amount of tissue necrosis of the pancreas due to acute injury after severe acute pancreatitis (SAP). Methods Twenty male SD rats were randomly divided into the model group and the sham operation group according to the random number table method, with 10 rats in each group. First, the SAP model was established by retrograde bile duct injection of sodium taurocholate in the model group, whereas the sham operation group received physiological saline injection. Fluid infusion began 2 hours later, twice a day, with an 8-hour interval, for 2 days. The traditional Chinese medicine Dachengqi Decoction without Decoction Granules was formulated into a suspension in proportion and administered by gavage once at 18 hours and once at 24 hours after the operation to ensure the blood volume of rats and reduce inflammatory damage. Normal drinking water was allowed 48 hours after modeling. After 72 hours, ordinary feed was given for feeding. The feeding lasted for 14 days (the total duration of the experiment was 17 days). The body weight, vitality status and stool characteristics of the rats were observed and recorded on the day of open feed feeding and 14 days later. Fourteen days after feeding, the animals were sacrificed and samples were collected for examination of blood glucose, fecal elastase and hematoxylin-eosin staining pathological scores. Results All 10 rats in the model group were successfully modeled with a 100% survival rate. The body weight of rats in the model group 14 days after ordinary feeding was lower than that on the day of open diet [(180.80±4.39) vs. (222.90±6.14) g, P<0.001], and lower than that of rats in the sham operation group 14 days later [(180.80±4.39) vs. (221.70±7.45) g, P<0.001]. Compared with the sham operation group, inflammatory cell infiltration injury still existed in the pancreatic tissue of the model group, and some pancreatic tissues showed pathologically related changes of chronic injury. The pathological score of the model group was higher than that of the sham operation group [7.5 (7, 9) vs. 0 (0, 0), P<0.001]; the blood glucose concentration increased [(13.000±1.531) vs. (8.070±0.851) mmol/L, P<0.001]. The secretion of fecal elastase, a metabolite of trypsin in vivo, was significantly decreased [(5.451±0.936) vs. (8.593±1.105) mg/mL, P<0.001]. Conclusion The use of short-term liquid supplementation, traditional Chinese medicine anti-inflammatory treatment, and early dietary stimulation can effectively combat early severe inflammatory damage in SAP, protect the life of model rats, and enable them to survive and experience digestive dysfunction, thus establishing an experimental animal model of digestive dysfunction in the late stage of SAP.
Objective To explore the feasibility of establishing a rabbit model of flail chest. Methods Flail chest model was eatablished in 12 New Zealand white rabbits after anesthesia and sterile surgery. The paradoxical movement of chest wall was recorded by the biological signal acquisition system, arterial blood was collected for blood gas analysis, the vital signs were recorded by electrocardiogram (ECG) and the lung tissue was taken for the pathological analysis at the end of the experiment. The effect of flail chest on the respiratory function of experimental animals was analyzed to evaluate the feasibility of establishing flail chest model. Results All surgeries were successful without mortality. The operation time was 41.42±7.08 min. Duration of endotracheal intubation was 79.33±12.21 min. Statistical results showed that the pH, partial pressure of arterial carbon dioxide (PaCO2) and base excess (BE) increased; while partial pressure of oxygen (PaO2) and oxygen saturation (SaO2) reduced. Pathological results showed that flail chest not intervented for a long period would lead to organic lesions. Conclusion The rabbit model of flail chest is feasible, safe, repeatable, easy and simple to handle. The animal is easy to access which is the foundation to study the disease process, recovery procedure and the efficacy after intervention.
ObjectiveTo establish a model of tracheomalacia in beagle dogs.MethodsSix healthy male beagles were selected with a weight of 12-15 kg and age of 12-18 months. The dog was placed in supine position after being anesthetized. Then midline incision was performed on dogs' cervical skin and main trachea was dissected. Six continuous cartilage rings separated from the tracheal wall were removed. Finally, the endotracheal mucosal was examined and the wound was sutured layer by layer. Different degrees of cartilage were removed to simulate different degrees of tracheomalacia. The beagle dogs were classified into two groups (n=3 in each group): a mild tracheomalacia (MTM) group (part of the cartilage near the trachea membrane was retained) and a severe tracheomalacia (STM) group (cartilage was removed as much as possible).ResultsThe dogs in the MTM group survived for a long time after the operation, showing symptoms of airway stenosis such as wheezing and coughing. The dogs were killed at postoperative week 2, and the pathological examination was performed. In the STM group, severe asphyxia occurred in the experimental animals after tracheal intubation removed, and all dogs died within 1 hour after surgery. Postoperative bronchoscopy revealed that the trachea of the MTM group dogs collapsed in the phase of inhalation, but it could maintain a certain patency. The trachea of the STM group dogs collapsed completely in the phase of inhalation. Postoperative X-ray showed that the diameter of the airway in the MTM group was reduced and trachea did not completely collapse. In the STM group, the trachea collapsed completely at the cartilage removed segment. Pathological examination showed that the cartilage in the MTM group was partially removed and tracheomalacia was obvious in the cartilage removed segment. In the STM group, most of the cartilage was removed with only few cartilages left.ConclusionThe clinical symptoms of tracheomalacia in different degrees can be simulated and repeatable. Animal models can be established by controlling the degree of removal of tracheal cartilage ring in dogs. This method provides a simple, repeatable and standardized large animal model for the treatment and transformation of tracheomalacia.
ObjectiveTo observe the effect of using tungsten drills to prepare mouse knee osteochondral injury model by comparing with the needle modeling method, in order to provide an appropriate animal modeling method for osteochondral injury research.MethodsA total of 75 two-month-old male C57BL/6 mice were randomly divided into 3 groups (n=25). Mice in groups A and B were used to prepare the right knee osteochondral injury models by using needles and tungsten drills, respectively; group C was sham-operation group. The general condition of the mice was observed after operation. The samples were taken at 1 day and 1, 2, 4, and 8 weeks after modeling, and HE staining was performed. The depth, width, and cross-sectional area of the injury site at 1 day in groups A and B were measured, and the percentage of the injury depth to the thickness of the articular cartilage (depth/thickness) was calculated. Toluidine blue staining and immunohistochemical staining for collagen type Ⅱ were performed at 8 weeks, and the International Cartilage Research Society (ICRS) score was used to evaluate the osteochondral healing in groups A and B.ResultsAll mice survived to the completion of the experiment. HE staining showed that group C had normal cartilage morphology. At 1 day after modeling, the injury in group A only broke through the cartilage layer and reached the subchondral bone without entering the bone marrow cavity; the injury in group B reached the bone marrow cavity. The depth, width, cross-sectional area, and depth/thickness of the injury in group A were significantly lower than those in group B (P<0.05). At 1, 2, 4, and 8 weeks after modeling, there was no obvious tissue filling in the injured part of group A, and no toluidine blue staining and expression of collagen type Ⅱ were observed at 8 weeks; while the injured part of group B was gradually filled with tissue, the toluidine blue staining and the expression of collagen type Ⅱ were seen at 8 weeks. At 8 weeks, the ICRS score of group A was 8.2±1.3, which was lower than that of group B (13.6±0.9), showing significant difference (t=?7.637, P=0.000).ConclusionThe tungsten drills can break through the subchondral bone layer and enter the bone marrow cavity, and the injury can heal spontaneously. Compared with the needle modeling method, it is a better method for modeling knee osteochondral injury in mice.
ObjectiveTo summarize the application research progress of animal models of hepatocellular carcinoma at home and abroad in recent years. MethodThe relevant literature on animal models of hepatocellular carcinoma at home and abroad in recent years was reviewed. ResultsAt present, the common animal models of hepatocellular carcinoma mainly included spontaneous animal model, induced animal model, gene modified animal model, transplanted animal model, and humanized animal model. The etiology, pathogenesis, and pathophysiological changes of various animal models were different. The selection of animal models of hepatocellular carcinoma depended on the type and purpose of research. ConclusionsVarious animal models of hepatocellular carcinoma have their own advantages and disadvantages. Researchers should choose different animal models according to their own research purposes to achieve the expected experimental purposes, so that more valuable research results of animal models of hepatocellular carcinoma can be applied to clinical practice, and finally these research results can be truly applied to diagnosis and treatment of hepatocellular carcinoma.
Objective To understand the advances in animal model and basic research of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS), and to provide new ideas for basic research and clinical application of ALPPS. Methods The literatures on the basic research and animal models of ALPPS were analyzed and reviewed. Results By March 2018, there were 19 articles related to ALPPS animal models published, including 11 rat model articles, 4 mouse model articles, 2 pig model articles, 1 rabbit model article, and 1 sheep model article. These models of ALPPS were mainly simulated in normal liver background (16 articles), only 2 mouse model of colorectal liver metastasis and 1 rat model of ALPPS under the sclerotic liver background on Chinese article. In cases of rat’s models, portal blood flow deprivation of 20%–90% was finished by portal vein ligation, and the liver was localized and segmented according to the ischemic line and the ligaments of the liver, and the liver partition was mostly sutured and electrocoagulated to stop bleeding. In the above models, remnant liver hyperplasia was observed after surgery. The main causes of hyperplasia were serum cytokines-mediated ［hepatocyte growth factor (HGF), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and so on］ enhancement of proliferative gene, and secondly preservation of the portal vein lobes to increase blood volume and to accelerate liver proliferation. ConclusionsThe animal model is the main tool to study the safety of ALPPS and liver regeneration, but there are still few studies in the models with liver cirrhosis and liver tumors. The mechanism of liver regeneration after ALPPS is still unclear, and more basic experiments and clinical cases are needed for further study.
Objective To observe the growth of orthotopic transplanted tumor in nude mice after stomatin-like protein 2 (SLP-2) expression decreased, and to further study the role of SLP-2 in the development and progression of esophageal squamous cell carcinoma. Methods Using RNA interference technique, esophageal squamous cell carcinoma cell lines with specific expression of SLP-2 and stable expression of luciferase were established. The healthy female nude mice with weight ranging from 19 to 22 g were randomly divided into 3 groups (n=12), 6 mice were used to establish subcutaneous xenografts, and the other 6 mice were used to establish the orthotopic transplanted tumor model (Group 1: cell infected with SLP-2-1 plasmid; group 2: cell infected with SLP-2-2 plasmid; group 3: cell infected with SHGFP plasmid). Index of the experiment end was weight loss and poor general situation in any mouse. Before the nude mice were sacrificed, the luciferase value of the tumor was detected by using in vivo imaging technique. After the nude mice were sacrificed, the primary tumor was removed for pathology examination. Results There was no significant difference in region of interest (ROI) value between the group 1 and group 2 (P=0.943). The ROI value for both groups 1 and 2 was significantly lower than that in the group 3 (P=0.002, P=0.000). The primary tumor infiltrated into the muscularis propria of esophageal was observed in all groups. Conclusion SLP-2 is involved in the development and progression of esophageal squamous cell carcinoma, and the decrease of SLP-2 expression can inhibit the growth of esophageal squamous cell carcinoma.
Objective To summarize the research progress on rodent models of cervical spinal cord injury (SCI). Methods The relevant domestic and foreign literature in recent years was reviewed, the methods of establishing the rodent models of cervical SCI and the evaluation methods of behavior, imaging, neuroelectrophysiology, and histology were summarized. Results Cervical SCI involves primary and secondary injuries. Primary cervical SCI can be simulated with contusion, contusion compression, fracture dislocation, spinal cord traction, and spinal cord transection; scondary cervical SCI can be simulated with photochemical model and excitotoxicity model. Certain evaluation methods such as behavior, imaging, neuroelectrophysiology, and histology are used to evaluation during model building and research. Conclusion Different rodent models of cervical SCI have different advantages and application directions, and it is critical importance for the study of cervical SCI to establish effective animal models.
ObjectiveTo discuss the feasibility of establishment of animal model of "functional" bicuspid aortic valve with swine and observe its effect on the wall shear stress inside the aorta. MethodsFour common Shanghai White Swine with body weight between 50 kg to 55 kg were selected. Under general anesthesia and cardiopulmonary bypass, the aortic transverse incision approach was used, continuous suture with 6-0 polypropylene to align the left and right coronary valve leaflets to create a bicuspid valve morphology. After the operation, echocardiography was used to observe the aortic valve morphology and the hemodynamic changes of the aortic valve orifice. The effect on the wall shear stress inside the aorta was studied with 4D-Flow magnetic resonance imaging (MRI). ResultsA total of 4 swine "functional" bicuspid aortic valve models were established, with a success rate of 100.0%. Echocardiography showed that the blood flow velocity of the aortic valve orifice was faster than that before the operation (0.96 m/s vs. 1.80 m/s). 4D-Flow MRI showed abnormally increased wall shear stress and blood flow velocity in the aorta of the animal models. After the surgery, in model animals, the maximal wall shear stress inside the ascending aorta was greater than 1.36 Pa, and the maximum blood flow velocity was greater than 1.4 m/s. ConclusionEstablishment of the animal model of "functional" bicuspid aortic valve in swine is feasible, scientific and reliable. It can be used in researches on evaluating the pathophysiological changes.