ABSTRACT
This paper mainly studied the effect of Xiyanping injection on the bacterial endotoxin lipopolysaccharide (LPS)-induced fever in rabbits, preliminarily investigated the mechanisms, and provided pharmacological basis for the clinical application. The rabbit model of endotoxin-induced fever was established by using LPS as the inducer; The changes of rectal temperature were measured; The levels of prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and phospholipaseA2 (PLA2) in the serum were measured; The levels of PGE2, cyclic adenosine monophosphate (cAMP), and arginine vasopressin (AVP) in cerebrospinal fluid as well as hypothalamus were detected. The animal welfare and experimental process are in accordance with the regulations of the Animal Ethics Committee of China Pharmaceutical University in this study. The results showed that Xiyanping injection (12.5, 25, and 50 mg·kg-1) could significantly reduce LPS-upregulated body temperature of rabbits, and the duration of action could reach 5.5-8.5 h. At the doses of 25 and 50 mg·kg-1, the antipyretic effect of Xiyanping injection was comparable to that of analgin injection (50 mg·kg-1). Furthermore, Xiyanping injection and analgin injection both reduced the levels of PGE2, IL-1β, TNF-α, and PLA2 in the serum of febrile rabbits to the varying degrees. In addition, Xiyanping injection also down-regulated the levels of PGE2, cAMP, and AVP in the hypothalamus, and PGE2 and cAMP in the cerebrospinal fluid. The level of AVP in the cerebrospinal fluid was up-regulated. This study indicated that Xiyanping injection could significantly improve the endotoxin-induced fever in rabbits, and mechanisms were closely related to the regulation of the levels of PGE2, TNF-α, IL-1β, PLA2, cAMP, and AVP in serum, hypothalamus, and cerebrospinal fluid.
ABSTRACT
Background The pathogenesis and management of human autoimmunity uveoretinitis is a focus in ophthalmology.For decades,a traditional experimental autoimmunity uveoretinitis (EAU) induced by pertussis toxin (PTX) was used for the basic investigation,which was thought to have a large deviation from the natural course of human autoimmunity uveoretinitis.Objective This study was to establish a new mice model of autoimmunity uveoretinitis which mimics the human autoimmunity uveoretinitis pathogenesis and offer a basis for the investigation and treatment of uveoretinitis.Methods Twenty 6-8 weeks old specific pathogen-free female C57BL/6 (H-2b) mice were randomized into normal control group,only endotoxin (lipopolysaccharide,LPS) induced uveitis group (endotoxin induced uveitis [EIU] group),interphotoreceptor retinoid-binding protein (IRBP1-20) +complete Freund adjuvant (CFA) induced uveoretinitis group (EAU group) and IRBP+CFA+LPS induced uveoretinitis group (LPS-EAU group).The mice of the EAU were only immunized with IRBP emulsified in CFA,and LPS-EAU group firstly were immunized with IRBP emulsified in CFA and then LPS was injected in the footpad of the mice on 7 days following immunization.The ocular pathological examination,histopathological scoring,delayed-type hypersensitivity and specific lymphocyte proliferating response were evaluated and compared with the EIU models,traditional EAU models without PTX and LPS-EAU models.The use and care of experimental animals complied with Regulation for the Administration of Affair Concerning Experimental Animals by State Science and Technology Commission.Results No inflammatory response was found in the iris,cilliary body and retina of mice in the normal control group.However,mild blood vessels dilation and fibrin exudation were seen in the iris and cilliary body of mice in the EIU group.In the EAU group,mild vasculitis and swelling of nerve fiber layer were exhibited in the retinas; while in the LPS-EAU group,severe disorder of retinal structure,infiltration of inflammatory cells and damage of photoreceptor were found under the optical microscope.The pathological score was 0 in the models of the normal control group and EIU group,0.5 score in the EAU group and 3.0 scores in the LPS-EAU group,with a significant difference in the pathological scores between the EAU group and the LPS-EAU group (U=16.246,P =0.001).The earthickness of the mice was (35.60±0.55) μm in the LPS-EAU group,and this value was significantly higher than (12.60±0.55) μm of the EIU group (q =23.003,P＜0.01),but closed to (34.80±0.84) μm of the EAU group (t =0.820,P＞0.05).The obvious cloning were seen and theradiation count per minute was (8 540.00 ±54.77)/min in the model mice of the LPS-EAU group,and that in the EAU group was (8 484.00±47.75)/min,without significant difference between them (q =56.634,P =0.069).Compared with the β particle number (2 050.00±50.00)/min in the EIU group,that of the LPS-EAU group was significantly elevated (q =195.683,P =0.000).Conclusions LPS injection can induce EAU in mice,and this model can better imitate the pathogenesis of human autoimmunity uveoretinitis.
ABSTRACT
In this study, the prophylactic effect of treatment of donor mice with naturally hypotoxic Ch. violaceum endotoxin on lethal GVHD induced in a murine P→F1 combination was observed. Treatment of the donors with the endotoxin inhibited GVH splenomegaly, attenuated clinical manifestations and improved survival rate and mean survival time of dead animals. In addition, treatment with the endotoxin could enhance the bone marrow cells to form CFU-S and promote the initial graftment rate of marrow allograft.
ABSTRACT
A typical smooth-form lipopolysaccharide (LPS) isolated from Salmonella abortus equi was fractionated into a S (smooth)-and a R (rough)-fraction and their serological and biological properties were investigated. It was shown that S- fraction expressed an O-antigenicity while R-fraction predominately a Rb-antigenicity. The R-fraction was endowed with higher bioactivities than the S-fraction in lethal toxicity, local Shwartzman reaction and pyrogenicity. Both S-and R-fractions were active in inducing mitogenicity to murine spleen cells. A reconstituted LPS preparation with fractionated S-fraction and a trace amount of R-fraction (1% of the original preparation) exhibited a same extent of lethal toxicity as that of the original one. Antr-Ra and -Rb antiserum with a liter of 1?4096 showed a .highly effective protection against the lethal challenge of LPS, indicating that the R-fraction in the natural LPS preparations plays a critical role to the lethality of LPS.
ABSTRACT
We had confirmed that treatment of donor mice with Ch. Violaceum endotoxin (lipopolysacchari-de,LPS)could inhibit GVHR. In this paper, its immunological mechanisms were explored. The results showed that the LPS could augment [3H] -TdR uptake by mouse spleen cells, but decrease their proliferative responses to LPS and Con A, and suppress unidirectional MLR and NK cell activity, with inhibitory rate of 64.5%, 66.1%, 51.7% and 59.3%, respectively, suggesting it had inhibitory effects on B, T lymphocytes and NK cells. In vitro experiments using mixtures of spleen cells from treated and normal mice showed there existed non-specific suppressor cell activity in LPS-and Con A-induced lymphocyte transformation but not in MLR and NK activity assays. That meant suppressor cells were not responsible for suppressive effects on T cells and NK cells which are thought to be main effector cells mediating GVHD.