不同剂量伊曲康唑制剂对犬血常规及肝肾功能的影响

旨在评价不同剂量伊曲康唑-环糊精制剂通过皮下注射途径对健康比格犬肝肾功能及血常规的影响。选用体重±10 kg的健康纯种比格犬32只,按试验要求随机分为4组,每组8只,建立稳定的生活制度。分别按照0.25 mg/kg、0.75 mg/kg和1.25 mg/kg剂量,皮下注射伊曲康唑制剂,3日1次,连续7次,对照组注射生理盐水。于试验过程中第0、5、10、15、19天采集相关样品,对犬临床表现、血常规指标、血液生化指标、尿常规指标及肝肾功能进行全面的评价。结果表明,给药组与对照组相比,除白细胞相关指标外,其余指标都在正常范围内。给药组在试验过程中均出现白细胞升高现象,但在试验结束后5 d内均恢复正常。因此,伊曲康唑-环糊精制剂作为犬皮下注射剂型,具有良好的安全性和耐受性,操作方便,动物依从性好,适合兽医临床应用。     

不同剂量环磷酰胺对昆明小鼠肝肾组织的损伤作用研究

为研究不同剂量的环磷酰胺对小鼠肝肾组织及功能的损害程度,试验选取40只5周龄健康雌性昆明小鼠,随机分为5组,除对照组外,其余4组小鼠连续3 d分别腹腔注射40、80、120及160 mg/（kg·BW）环磷酰胺溶液,注射后第7天采集肝脏和肾脏组织样品及血清,制备石蜡组织切片及透射电镜切片,观察肝脏和肾脏的组织学变化,检测血清中甘胆酸（CG）、胆碱酯酶（ChE）、血清前白蛋白（PA）、总胆汁酸（TBA）、谷丙转氨酶（ALT）、谷草转氨酶（AST）、尿素氮（BUN）、血清肌酐（SCr）、尿酸（UA）含量/活性。结果显示,环磷酰胺可引起小鼠肝肾组织病理损害,呈剂量依赖性,肝脏比肾脏更早出现损伤。石蜡切片及透射电镜切片观察结果显示,环磷酰胺对肝脏的毒性作用主要表现在肝索紊乱、肝血窦扩张、微胆管淤胆、门管区及中央静脉周围炎性细胞浸润及纤维增生、组织间出血、肝细胞出现脂肪变性及气球样变性,凋亡及坏死细胞增多。肾脏组织损伤主要表现在出血及纤维增生,肾小管上皮细胞胞浆空泡样变、线粒体损伤、核固缩,上皮细胞基底膜增厚。环磷酰胺对膀胱的损害不严重。与对照组相比,40~160 mg/（kg·BW）剂量组小鼠血清中ChE活性及PA水平,120~160 mg/（kg·BW）剂量组AST活性,80~160 mg/（kg·BW）剂量组BUN水平及80 mg/（kg·BW）剂量组UA水平均显著升高（P<0.05）;其余生化指标与对照组差异不显著（P>0.05）。以上结果表明,环磷酰胺注射剂量在80~120 mg/（kg·BW）时可引起昆明小鼠肝脏和肾脏组织及细胞明显的病理损伤。该研究结果可为选择合适的环磷酰胺注射剂量用以制备动物肝脏免疫抑制模型提供试验依据。     

Sarcocystid organisms found in bile from a dog with acute hepatitis: a case report and review of intestinal and hepatobiliary Sarcocystidae infections in dogs and cats

Sarcocystidae is a family of coccidian protozoa from the phylum Apicomplexa that includes Toxoplasma, Neospora, Sarcocystis, Hammondia, and Besnoitia spp. All species undergo a 2‐host sexual and asexual cycle. In the definitive host, replication is enteroepithelial, and infection is typically asymptomatic or less commonly causes mild diarrhea. Clinical disease is most frequently observed in the intermediate host, often as an aberrant infection, and is mostly associated with neurologic, muscular, or hepatic inflammation. Here, we review the literature regarding intestinal Sarcocystidae infections in dogs and cats, with emphasis on the life cycle stages and the available diagnostic assays and their limitations. We also report the diagnostic findings for an 11‐year‐old dog with acute neutrophilic hepatitis, biliary protozoa, and negative biliary culture. Although Toxoplasma and Neospora IgG titers were both high, PCR for these 2 organisms was negative for bile. The organisms were identified by 18S rDNA PCR as most consistent with Hammondia, either H heydorni or H triffittae. This is the first report of presumed Hammondia organisms being found in canine bile.     

Effects of butafosfan with or without cyanocobalamin on the metabolism of early lactating cows with subclinical ketosis

Fifty‐one dairy cows with subclinical ketosis were used to investigate the effects of butafosfan alone or in combination with cyanocobalamin on metabolism. Treatments included i.v. injection of 10 ml/100 kg of body weight with butafosfan (BUT) or combined cyanocobalamin with butafosfan (BUTCO) at a similar concentration as in Catosal^®. Control cows (CON) received a 0.9% saline solution. Cows were injected on days 1–3 at 22.3 ± 0.7 days post‐partum. Milk production and composition were not affected by the treatments. In plasma, CON cows had a significantly higher plasma NEFA concentration (0.59 ± 0.03 mm ) across the study period than BUTCO cows (p < 0.05; 0.42 ± 0.03 mm ), whereas the plasma NEFA concentration of BUT was intermediate (0.52 ± 0.03 mm ) but not significantly different from CON. Both BUTCO and BUT cows had lower (p < 0.05) plasma BHBA concentrations (1.02 ± 0.06 mm and 1.21 ± 0.06 mm , respectively) across the study period than CON (1.34 ± 0.06 mm ). Plasma glucose was not different between treatments, but plasma glucagon concentrations were consistently high in BUT compared to BUTCO and CON. Lowest post‐treatment glucagon levels were observed in BUTCO. Hepatic mRNA abundance of liver X receptor α, a nuclear receptor protein involved in lipid metabolism, was higher in BUTCO compared to BUT and CON (p < 0.05) on day 7. Furthermore, on day 7, the mRNA abundance of beta‐hydroxybutyrate dehydrogenase 2 was higher in BUTCO compared to BUT and CON (p < 0.01). In conclusion, injections of combined cyanocobalamin with butafosfan post‐partum in early lactation ketotic dairy cows act on lipid metabolism with effects on plasma metabolites, most likely mediated via modified activity of key factors in the liver. Results indicate that the application of butafosfan only in combination with cyanocobalamin exhibits the expected positive effects on metabolism.     

Mechanism of Fuzilizhong decoction alleviating inflammatory damage of rats with non-alcoholic fatty liver disease

AIM To observe the effect of Fuzilizhong decoction on the inflammatory damage of non-alcoholic fatty liver disease （NAFLD） rats and to explore its mechanism. METHODS SPF male SD rats were randomly divided into 6 groups： control group, model group, high dose （20 mg·kg^-1·d^-1）, middle dose （10 mg·kg^-1·d^-1）, low dose （5 mg·kg^-1·d^-1） Fuzilizhong decoction group and Yishanfu （30 mg·kg^-1·d^-1）group, 8 rats in each group. A NAFLD rat modelwas established by intragastric administration of fat emulsion for 4 weeks. Then the drug was given for 4 weeks in each treatment group. HE staining was performed to observe the histopathological changes of the rat liver.The serum levels of interleukin-2（IL-2）, IL-6 and tumor necrosis factor-α（TNF-α） were measured by ELISA. The expression of toll like receptor 4（TLR4） and NF-κB p65 in liver tissues at mRNA and protein levels was determined by RT-qPCR and Western bolt,respectively. RESULTS Compared with control group, the inflammatory damage of liver tissue was more serious, the serum levels of IL-2, IL-6 and TNF-α, the mRNA expression TLR4 and NF-κB p65 in liver tissues were significantly increased in model group（P<0.05）. However, compared with model group, the liver pathological changes in each treatment group were significantly relieved, the serum levels of IL-2, IL-6 and TNF-α, the mRNA expression of TLR4 and NF-κB p65 in liver tissues were significantly reduced（P<0.05）.In addition, the changes of TLR4 and p-NF-κB p65 protein levels in liver tissue were consistent with the changes of TLR4 and NF-κB p65 mRNA. CONCLUSION Fuzilizhong decoction attenuates the inflammatory damages of NAFLD in rats by inhibiting TLR4/NF-κB p65 signaling pathway.