ABSTRACT
<p><b>OBJECTIVE</b>To develop an animal model of thrombosis and blood stasis syndrome in rats by using lipopolysaccharide (LPS) in combination with carrageenan (Ca).</p><p><b>METHOD</b>SD rats in control group were randomly divided into control group and model group (LPS/Ca treatment). The rats in model group were firstly treated with Ca ip, and followed by LPS iv sixteen hours later. The rats in control group were given normal saline (NS). The moment of LPS iv was served as 0 h for the observation. The ear microcirculation, blood rheology parameters (whole blood viscosity etab, plasma viscosity etap and platelet aggregation PA), cruor parameters (thrombin time TT, prothrombin time PT, and partial thromboplastin time APIT) and inflammation factors (TNFalpha, IL-6) were observed at different time after treatment.</p><p><b>RESULT</b>LPS/Ca combinatory treatment can induce a stable and repeatable thrombosis animal model. The thrombus can be observed on the tails of rats by naked eyes, and can be quantitatively measured without necessary of autopsy. Obstacle in microcirculation, increase in whole blood viscosity (etab) and a change of platelets aggregation (PA) rate were observed after LPS/Ca treatment. Cruor parameters were significantly prolonged due to large consumption of cruor factors and platelets. The concentration of inflammation factors TNFalpha and IL-6 in blood was obviously increased at the early stage of the model. The results indicate that this animal model has the characteristics of blood stasis syndrome caused by pyrogen and toxin accompanied by thrombosis.</p><p><b>CONCLUSION</b>LPS/Ca combinatory treatment can induce a easily practicable and repeatable animal model characterized as thrombosis and blood stasis syndrome</p>
Subject(s)
Animals , Male , Rats , Blood Coagulation Disorders , Blood , Blood Viscosity , Carrageenan , Disease Models, Animal , Interleukin-6 , Blood , Lipopolysaccharides , Microcirculation , Platelet Aggregation , Prothrombin Time , Random Allocation , Rats, Sprague-Dawley , Thrombin Time , Thrombosis , Blood , Tumor Necrosis Factor-alpha , MetabolismABSTRACT
<p><b>OBJECTIVE</b>The acute toxic effects of Aristolochia manshuriensis (GMT) and the total aristolochic acids (TA) were compared in mice with aristolochic acid A (AA) as the dose standard. The dose relationship of the renal toxicity induced by Aristolochia manshuriensis was determined.</p><p><b>METHOD</b>A single dose of GMT extract or TA was given intragastrically to mice at different doses. LD50 values, the blood levels of BUN, Cr and ALT were measured. A histomorphological study was also performed in livers and kidneys of mice.</p><p><b>RESULT</b>LD50 value of GMT extract was 4.4 g x kg(-1) which was equivalent to 40 mg x kg(-1) as calculated by the content of AA in GMT extract, and this value was comparable with LD50 obtained from TA given intragastrically in mice (equivalent to 33 mg x kg(-1) of AA for male and 37 mg x kg(-1) for female). GMT extract caused a significant increase in blood BUN and Cr and an obvious morphological change in kidney in a dose-dependent manner at doses of AA 4.5 mg x kg(-1) and above. Liver damage, characterized by both an increase in blood level of AST and histomorphological change, was observed at doses of AA 25 mg x kg(-1) and above. All changes were in proportion to the doses of AA.</p><p><b>CONCLUSION</b>GMT causes both renal and liver toxicity. The dose leading to nephrotoxicity is much lower than that inducing hepatatoxicity. Aristolochic acids existed in GMT are the main toxic components to cause renal toxicity which is a crucial cause to result in death. The lethality and nephrotoxicity of GMT is in proportion to the doses of AA.</p>
Subject(s)
Animals , Female , Male , Mice , Alanine Transaminase , Blood , Aristolochia , Chemistry , Aristolochic Acids , Toxicity , Aspartate Aminotransferases , Blood , Blood Urea Nitrogen , Creatinine , Blood , Dose-Response Relationship, Drug , Drugs, Chinese Herbal , Toxicity , Kidney , Pathology , Lethal Dose 50 , Liver , Pathology , Mice, Inbred ICR , Random AllocationABSTRACT
The article summarized the general situation of the study on the renal toxicity caused by aristolochic acids (AAs) and Chinese herbs containing AAs. The renal lesion induced by AAs and Chinese herbs containing AAs locates mainly in renal tubules, and glomeruluses have no obvious histological change. The short term administration of large doses causes acute renal epithelia denaturalization and tubular necrosis, but the long-term administration may result in chronically progressive interstitial fibrosis of the kidney. Renal failure may occur following both acute and chronic renal lesion. The renal function should be strictly monitored while one is using the Chinese herbs containing AAs, and the dosage and duration for the treatment must be limited to prevent renal toxicity.