Effects of Jianpi Qutan Huayu Prescription on Inflammatory Response of Atherosclerosis in Mini-pigs Based on NOX5-ERK1/2 Signaling Pathway / 中国中医药信息杂志

Objective To observe the effects of Jianpi Qutan Huayu Prescription on oxidative stress and inflammatory response in mini-pigs with atherosclerosis(AS);To explore its mechanism based on the NOX5-ERK1/2 signaling pathway.Methods Twelve Bama mini-pigs were randomly divided into control group,model group,and Jianpi Qutan Huayu Prescription low-and high-dosage groups,with 3 pigs in each group.A high-fat diet was used to feed for 24 weeks to construct an AS model,and the treatment group was also supplemented with Jianpi Qutan Huayu Prescription in the feed.The general condition of mini-pigs(body length,abdominal circumference,body mass,food intake,and fecal water content)was measured at week 0,16,and 24 of administration,HE staining was used to observe the morphology of aortic tissue,while oil red O staining was used to observe lipid deposition in aortic and myocardial tissue,transmission electron microscopy was used to observe the ultrastructure of aortic tissue,and a fully automated biochemical analyzer was used to detect serum contents of TC,HDL-C,and LDL-C.ELISA was used to detect the contents of serum reactive oxygen species(ROS),interleukin(IL)-6,IL-10,tumor necrosis factor(TNF)-α,hypersensitivity-C-reactive protein(hs-CRP),vascular cell adhesion molecule-1(VCAM-1),and intercellular adhesion molecule-1(ICAM-1).Western blot was used to detect the expressions of NADPH oxidase 5(NOX5),extracellular signal regulated kinase 1/2(ERK1/2),p-ERK1/2,VCAM-1,and proliferating cell nuclear antigen(PCNA)proteins.Results Compared with the control group,the abdominal circumference,body mass,and food intake of mini-pigs in the model group increased at 16 and 24 weeks(P<0.01),there was significant thickening of the inner membrane of aorta,destruction of endothelial cells,lipid deposition,edema of smooth muscle cells,and significant swelling of mitochondria,serum TC,LDL-C contents and the contents of ROS,IL-6,IL-10,TNF-α,hs-CRP,VCAM-1,and ICAM-1 increased,while the content of HDL-C decreased(P<0.01);the expressions of NOX5,p-ERK1/2,VCAM-1,and PCNA proteins in aortic tissue increased(P<0.01).Compared with the model group,Jianpi Qutan Huayu Prescription low-and high-dosage groups showed a decrease in abdominal circumference,body mass,and food intake at 16 and 24 weeks(P<0.05,P<0.01),the plaque area and lipid deposition were reduced,and the damage to endothelial cells was alleviated,serum TC,LDL-C contents and the contents of ROS,IL-6,IL-10,TNF-α,hs-CRP,ICAM-1,and VCAM-1 decreased,and the content of HDL-C increased(P<0.01,P<0.05);the expressiond of NOX5,p-ERK1/2,VCAM-1,and PCNA proteins in aortic tissue decreased(P<0.01,P<0.05).Conclusion Jianpi Qutan Huayu Prescription can effectively alleviate AS in mini-pigs,and its mechanism may be related to inhibiting the activation of the NOX5-ERK1/2 signaling pathway and alleviating oxidative stress-induced inflammatory response.

Methods for Creating Medium and Large Animal Models of Peripheral Atherosclerosis / 中国医学科学院学报

Atherosclerosis (AS) is the main pathological basis for the occurrence of many vascular diseases and has a strong association with metabolic syndrome. Peripheral arterial diseases caused by AS have high morbidities and mortalities but lack still effective treatment. AS animal models are highly valuable for research on peripheral arteriosclerotic diseases. While small and medium AS animal models based on high-fat feeding and balloon injuries have been successfully established,few literatures have described the creation of large animal models for AS treatment. This article elucidates the current methods for creating medium and large animal models of peripheral atherosclerotic disease,with an attempt to further promote the clinical translation of AS treatment research.

Commonly Used Vomiting Animal Models / 中国实验方剂学杂志

Vomiting is a common clinical symptom. Long-term severe vomiting could seriously reduce the life quality of patients, so it is necessary to be intervened with antiemetic drugs. Traditional Chinese medicine has a long history in the treatment of vomiting with remarkable a curative effect. It has the advantages of multi-component, multi-target and multi-system synergistic antagonism. However, due to the active substance and unclear mechanism, it is urgent to adopt an internationally recognized vomiting model system to evaluate the antiemetic characteristics, elucidate the vomiting mechanism, and provide reference for better clinical application. Therefore, this paper systematically introduces several vomiting animal models that are widely used at home and abroad. According to the authors' own experimental experience, this paper focuses on the rat and mice pica models for reference of relevant researchers. Specifically, ferrets are an internationally recognized ideal vomiting animal model, and the golden standard for evaluating the effects of antiemetic drugs, suncus murinus is the smallest mammalian vomiting model. Rodents have no vomiting reflexes, but studies have shown that its pica behavior is equivalent to the vomiting behavior of other species. Because the easy availability and operation, the model has been promoted and applied in mainland China. Guizhou mini-pig model is a self-developed medium-sized mammalian vomiting model with a similar anatomical structure and vomiting characteristics to human, and worthy of popularization and application. In conclusion, different vomiting models have their own characteristics that need to be optimized according to the purpose of experiments and samples.

Immunogenicity and safety of Sabin IPV vaccine in Banna mini pigs / 中国实验动物学报

Objective To evaluate the immunogenicity and safety of inactivated poliovirus vaccine derived from Sabin strain (sIPV) in Banna mini pigs, and to provide experimental evidence for the new animal model. Methods sIPV vaccines which are listed at Institute of Medical Biology at Chinese Academy of Medical Sciences were used in this study. The groups of intramuscular sIPV and the wild strain IPV injections (IPV derived from wild strain, wIPV) were designed, and the saline group was used as a negative control group. The Banna mini pigs in various groups were immunized at 0, 1 and 2 months. Blood samples were collected before immunization and on days 30 after each immunization. Levels of neutralizing antibodies were tested for evaluating immunogenicity. The safety was evaluated by observation of the status and weight of mini pigs. Results After the three dose immunization schedules in the Banna mini pigs, the seroconversion rates of type Ⅰ,Ⅱ and Ⅲ sIPV experimental groups and wIPV group were all up to 100%. The neutralizing antibody levels in all the three types were much higher than the protective titer 1: 8. The weight of mini pigs increased after vaccination. Conclusions The sIPV vaccine has good immunogenicity and safety in Banna mini pigs. Banna mini pigs could be a new animal model for evaluation of sIPV vaccine.

Correlation between Organ Weight and Body Weight in Outbred Wuzhishan Mini-Pigs / 中国实验动物学报

Objective To measure the organ weight and body weight of outbred Wuzhishan mini-pigs (WZSP), and calculate the organ coefficient and the linear and multiple linear regression equations between body weight and major organ weights. Methods 30 common WZSP (16 males and 14 females) were chosen,the body weight and 7 organ weights were determined, and the organ coefficients were calculated. The organ coefficients between males and females were compared. The correlation and regression analysis was performed using the SAS software. Results The coefficient of heart had remarkably significant difference between males and females (P<0.05).The linear analysis showed that there were apparent linear correlations between body weight and all the organ weights except for the stomach of males and the lung of females.The weights of liver and kidney showed great influence on the body weight of males, while the body weight of females relied on the weights of heart, liver and kidney greatly. Conclusion Differences of organ coefficients are not significant between males and females,and there are linear relationships between body weight and some major organ weights.

Experimental study on how brain-dead state affects the heart structure and function of Ba-Ma mini pigs and the mechanism / 中国病理生理杂志

AIM: To investigate how brain-dead state affects the heart structure and function and the effect of PKC-? in BA-Ma mini pigs.METHODS: Ten Ba-Ma mini pigs were randomized into 2 groups: brain-dead group(n=5),and control group(n=5).The brain-dead model was made by increasing intracranial pressure,while the control group was maintained anesthesia for 24 h.The concentrations of cTnT,TNF-?,IL-1? and IL-6 in serum were determined at 6,12 and 24 h after brain death.At 24 h,heart tissues were observed by HE staining and electron microscope.The expression of PKC-? was detected by immunohistochemistry and RT-PCR.RESULTS:(1) Histological changes of myocardium: flaky bleeding under endocardium and dissolution of myocardium were found in optical microscope.In electron microscope dropsical mitochondria and confluent muscle fiber were found.(2) Changes of serum cTnT: serum cTnT for brain-dead group began to increase gradually since 6 h,and were significantly higher at each time point than those in control group(P