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Abstract Introduction The relationship between humidity and systemic lupus erythematosus (SLE) has yielded inconsistent results in prior research, while the effects of humidity on lupus in animal experiments and its underlying mechanism remain inadequately explored. Methods The present study aimed to investigate the impact of high humidity (80 ± 5%) on lupus using female and male MRL/lpr mice, with a particular focus on elucidating the role of gut microbiota in this process. To this end, fecal microbiota transplantation (FMT) was employed to transfer the gut microbiota of MRL/lpr mice under high humidity to blank MRL/lpr mice under normal humidity (50 ± 5%), allowing for an assessment of the effect of FMT on lupus. Results The study revealed that high humidity exacerbated lupus indices (serum anti-dsDNA, ANA, IL-6, and IFN- g, and renal pathology) in female MRL/lpr mice but had no significant effect on male MRL/lpr mice. The aggravation of lupus caused by high humidity may be attributed to the increased abundances of the Rikenella, Romboutsia, Turicibacter, and Escherichia-Shigella genera in female MRL/lpr mice. Furthermore, FMT also exacerbated lupus in female MRL/lpr mice but not in male MRL/lpr mice. Conclusion In summary, this study has demonstrated that high humidity exacerbated lupus by modulating gut microbiota in female MRL/lpr mice. The findings underscore the importance of considering environmental factors and gut microbiota in the development and progression of lupus, particularly among female patients.
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Aim: To explore the role of paeoniflorin-6'- O-benzenesulfonate (CP-25) in MRL/lpr mice and the regulating action on Thl7 cell differentiation. Methods MRL/lpr mice were randomly assigned to five groups as follows; model group, CP-25 (20, 40, 80 mg · kg
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Objective This study aims to investigate the variation of neutrophil extracellular traps (NETs) in animal model of staphylococcus aureus (SA) infected systemic lupus erythematosus (SLE) MRL/Lpr mouse.Methods The infection model was developed by injecting the Staphylococcus Aureus in the mouse tail vein.The Staphylococcus Aureus load of the serum and kidney was detected by enzyme-linked immuno sorbent assay (ELISA).The level of NETs complex in the serum was detected by Cell-Death-Elisa-Plus-Kit and anti-myeloperoxidase (MPO) antibody.The kidney NETs formation was tested with the immunofluorescence.Statistical program for social sciences (SPSS) 17.0 software and Image Pro Plus statistical software were used for analysis.Comparisons between groups were made using unpaired t test for normally distributed numerical data,nonparametric test for non-normally distributed numerical data,and single factor analysis (ANOVA) for variance.Results The incidence of walking instability,purulent exudate in eyes and death was 2/6,1/6,1/6 respectively in Staphylococcus Aureus-infected MRL/Lpr mice,However,The control group had no death and related symptoms.The Staphylococcus Aureus load of the serum was higher in MRl/lpr mice when compared to the control group [(106.79±23.39) ng/ml vs (48.82±11.49) ng/ml,U=2.739,P＜0.05] after Staphylococcus Aureus infection.The control group had a higher NETs level [(2.24±0.15) vs (1.64±0.08),U=2.882,P＜0.05],however,all the MRL/Lpr mice had no significant change of the NETs level [(2.63±0.61) vs (2.65 ±0.260),U=0.548,P＞0.05] after Staphylococcus Aureus infection.Conclusion After infected by the Staphylococcus Aureus,more symptoms,higher death rate and higher Staphylococcus Aureus load of the serum present in the MRlL/lpr mice than the control group.While,there's none significant change of the NETs level in Staphylococcus Aureus-infected MRLL/lpr mice.This suggests that the dyspoiesis of NETs is present in Staphylococcus Aureus-infected MRL/lpr mice.
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Objective To explore the immune mechanism in the systemic lupus erythematosus MRL/lpr mice at different months of age, and to provide the basis for research of its pathogenesis. Methods 3-,4-,5- and 6-month old female MRL/lpr mice, and wild type C57 female mice were used in this study, 10 mice per each group. Their organ coefficients were determined. ELISA was performed to detect the serum levels of double stranded DNA(ds-DNA) antibody. The interleukins IL-2,IL-4,IL-17 and tumor necrosis factor-α(TNF-α)in spleen tissue were detected. Flow cytometry was used to assess the content of spleen lymphocyte CD3 cells and CD4/CD8 cell ratio. Results Compared with the 3-month old wild-type C57 mice,the spleen coefficient,the blood concentration of ds-DNA antibody,IL-2 and TNF-α in the 3- to 6-month old MRL/lpr mice were significantly increased(P < 0.05). There was no significant difference between the concentrations of interleukin IL-4(P> 0.05). The blood concentration of IL-17 in the 5- and 6-month old MRL/lpr mice was significantly lower(P < 0.05 or P < 0.01)than that in the 3-month old MRL/lpr mice. The rest indexes of MRL/lpr mice showed no obvious changes or significant difference in the mice at different ages. Compared with the 3-month old C57 mice,the spleen CD3 lymphocyte concentration in the MRL/lpr mice was significantly decreased(P< 0.01). With the increasing age, the CD3 lymphocyte concentration and D4 +/CD8 +cell ratio in the MRL/lpr mice were decreased, however, showing a non-significant difference(P ﹥0.05). Conclusions The data obtained in this study indicate that 3-month old lupus MRL/lpr mice have already immune injury,increasing with the increase of age of the mice.
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AIM:To investigate the effect of arsenic trioxide (ATO) on T-bet/GATA3 signal pathway in MRL/lpr mice.METHODS:MRL/lpr mice and C57BL/6J mice at the age of 20 weeks were chosen and then divided in 2 different sub-groups,respectively.The mice in 2 sub-groups received ATO (0.4 mg · kg-1.d-1) and sodium chloride (NS,volume weight-determined) by intraperitoneal injection respectively for 2 months.Afterward,the spleens were isolated fron the MRL/lpr and C57BL/6J mice under pathogen-free condition and the suspensions were prepared.The mRNA level of T-bet,GATA3,IFN-γ,IL-4 and the mRNA ratio of T-bet/GATA3 were detected by RT-qPCR.The protein expression of T-bet and GATA3 was determined by Western blot.The serum levels of IFN-γ and IL-4 were measured by ELISA.RESULTS:The mRNA and protein levels of T-bet,IFN-γand the mRNA ratio of T-bet/GATA3 in NS group of MRL/lpr mice were higher than those in NS group of C57BL/6J mice (P ＜0.05).However,the GATA3 and IL-4 were lower in NS group of MRL/lpr mice in both mRNA and protein level (P ＜ 0.05).In MRL/lpr mice,the mRNA and protein levels of T-bet,IFN-γ and the mRNA ratio of T-bet/GATA3 were lower in ATO group compared with NS group (P ＜ 0.05),no difference was found in GATA3 and IL-4.No difference of the indexes mentioned above between ATO group and NS group in C57BL/6J mice was observed.CONCLUSION:ATO may affect the signaling pathway of T-bet/GATA3 to down-regulate the mRNA expression and the protein secretion of IFN-γ by decreasing the expression of T-bet in MRL/lpr mice.
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AIM:To investigate the effect of arsenic trioxide (ATO) on T-bet/GATA3 signal pathway in MRL/lpr mice.METHODS:MRL/lpr mice and C57BL/6J mice at the age of 20 weeks were chosen and then divided in 2 different sub-groups,respectively.The mice in 2 sub-groups received ATO (0.4 mg · kg-1.d-1) and sodium chloride (NS,volume weight-determined) by intraperitoneal injection respectively for 2 months.Afterward,the spleens were isolated fron the MRL/lpr and C57BL/6J mice under pathogen-free condition and the suspensions were prepared.The mRNA level of T-bet,GATA3,IFN-γ,IL-4 and the mRNA ratio of T-bet/GATA3 were detected by RT-qPCR.The protein expression of T-bet and GATA3 was determined by Western blot.The serum levels of IFN-γ and IL-4 were measured by ELISA.RESULTS:The mRNA and protein levels of T-bet,IFN-γand the mRNA ratio of T-bet/GATA3 in NS group of MRL/lpr mice were higher than those in NS group of C57BL/6J mice (P ＜0.05).However,the GATA3 and IL-4 were lower in NS group of MRL/lpr mice in both mRNA and protein level (P ＜ 0.05).In MRL/lpr mice,the mRNA and protein levels of T-bet,IFN-γ and the mRNA ratio of T-bet/GATA3 were lower in ATO group compared with NS group (P ＜ 0.05),no difference was found in GATA3 and IL-4.No difference of the indexes mentioned above between ATO group and NS group in C57BL/6J mice was observed.CONCLUSION:ATO may affect the signaling pathway of T-bet/GATA3 to down-regulate the mRNA expression and the protein secretion of IFN-γ by decreasing the expression of T-bet in MRL/lpr mice.
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Objective:To observe the effect of CD40 siRNA on the changes in kidney,urinary protein and complement C3 of MRL/Lpr mice and explore its therapy on lupus nephritis.Methods: 16 female MRL/Lpr mice were randomly divided into control group,empty vector group,CD40-siRNA1 group and CD40-siRNA2 group.The vectors expressing siRNA against CD40 were injected by tail veil into MRL/Lpr mice,while MRL/Lpr mice in control group and empty vector group were injected with the same dose of PBS and pGFP-V-RS vector respectively.There were six times injection and every one day.The 24 hours urine output was gathered 24 hours before mice were killed.Fourteen days following administration,these mice were killed,tissue sections of kidney were observed if the signal of siRNA were expressed in kidney.The expression levels of CD40 mRNA and protein in kidney tissue of MRL/Lpr mice were detected by RT-PCR and immunohistochemistry methods respectively.At the same time,the pathological changes of the kidney were observed by haematoxylin-eosin ( HE) staining method.The 24 h urinary protein content was detected using the method of coomassie brilliant blue and the expression levels of complement C3 in serum were detected by Immunoturbidimetric assays.Results:The vector of CD40-siRNA was expressed in kidney of MRL/Lpr.The expression levels of CD40 mRNA and protein in kidney were lower in CD40-siRNA1 group and CD40-siRNA2 group than control group and empty vector group on the 14th day after last injection ( P<0.05).The inflammatory cells infiltration of kidney and some glomerular volume were significantly reduced in CD40-siRNA1 group and CD40-siRNA2 group than control group and empty vector group.The renal tubular swelling was alleviated in CD40-siRNA1 group and CD40-siRNA2 group than control group and empty vector group.The levels of 24 hours urinary protein were lower and the levels of complement C3 were higher in CD40-siRNA1 group and CD40-siRNA2 group than control group and empty vector group ( P<0.05). Conclusion:CD-40 siRNA can suppress the expression levels of CD40 mRNA and protein and decrease inflammatory cells infiltration in kidney of MRL/Lpr.Meanwhile after suppressing expression of CD40 mRNA and protein, it can reduce the content of 24 hours urinary protein and elevate the level of complement C3 in serum,which CD-40 siRNA can delay progress of the disease and protect kidney,so that it has therapy effect on lupus nephritis.
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ObjectiveToclarifytheprotectiveactionofaChinesemedicine,Jie-Du-Qu-Yu-Zi-Shen prescription, on the lupus nephritis in MRL/lpr mice through the TLR9-MyD88-NF-κB signaling pathway .Methods Thirty MRL/lpr mice were randomly divided into model group , prednisone group , and traditional Chinese medicine ( TCM) group (n=10).Each treatment group received appropriate treatment or drug therapy for 8 weeks.The pathological changes of mouse renal tissues in the three groups were examined and compared using HE , PAS, and Masson staining .Real-time PCR was performed to compare the expression of TLR-9, MyD88, NF-κBm RNA mRNA in each group of the mice . Results Compared with the model group , the Chinese medicine Jie-Du-Qu-Yu-Zi-Shen prescription significantly improved the renal pathological tissue damages in the MRL/lpr mice.Real-time PCR assay showed that the expression levels of TLR-9, MyD88, NF-κB mRNA in the TCM group were significantly lowered (P0.05 ) .Conclusions Jie-Du-Qu-Yu-Zi-Shen prescription has protective effect on the kidney of MRL /lpr mice, alleviating its pathological changes , and delaying the disease course, probably, through inhibiting the TLR-9-MyD88-NF-κB signaling pathway in the kidneys of MRL/lpr mice.
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Objective To investigate the efficacy and adverse reactions of half-dose glucocorticosteroid and cytoxan,combined with leflunomide for the treatment of lupus nephritis (LN) of MRL/lpr mice,and provide experimental evidences for LN therapy.Methods Twenty-eight 10-week-old MRL/lpr mice were randomly divided into four groups:Group A,blank control group; Group B,classical control group; Group C,full-dose control group; Group D,half-dose treatment group,with 7 mice in each group.The therapeutic efficacy and side reactions in the four groups were observed and compared before and 12 weeks after treatment.Statistical analysis was conducted with one-way ANOVA,q test and Pearson's correlation analysis.Results The serum anti-double stranded DNA (anti-dsDNA) antibody titers (0.43±0.16,0.32±0.09,0.44± 0.18,1.95±0.19) U/ml,serum creatinine level (1.63±0.63,0.40±0.23,0.82±0.21,10.86±2.17) mg,24-hour urine protein excretion level (71±8,60±5,68±3,121±10) μmol/L and renal pathological changes in group B,C,D were significantly improved than those of the group A (P＜0.05) after 12 weeks treatment.There was no significant difference in the efficacy between group B,C,and D (P＞0.05).The incidence of adverse reactions in group D was significantly lower than that in other groups (P＜0.05).Conclusion Multi-target therapy,such as half-dose prednisone and CTX,combined with leflunomide can effectively control lupus disease activity with less side effects.This regimen is cheap,safe and effective for the treatment of LN in MRUL/lpr mice.This study has provided animal evidences for this multi-target therapy for LN.
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Objective To explore the effects of Jiedu Quyu Ziyin Recipe (JQZR) on the apoptosis and expressions of bcl-2 and bax mRNA of peripheral-blood lymphocyte in MRL/lpr mice. Methods 80 MRL/lpr mice were randomly divided into model group,TCM group, Western medicine group and TCM and Western medicine group,20 mice in each group, meanwhile,20 Kunming mice were selected as normal group, then intragastrically administered normal sodium, JQZR apozem, prednisone suspension and JQZR apozem and prednisone suspension, 0. 5ml every time,once daily for 12 weeks respectively. At the end of the 12th week, peripheral-blood lymphocytes of every mice purified by gradient centrifugation were cultivated for 48 hours ,then the apoptosis was detected by flow cytometry. Furthermore,the expressions of bcl-2 and bax mRNA of peripheral-blood lymphocyte were detected by RT-PCR. Results At Oh or 48h,the apoptosis ratios of PBLC in normal group, TCM group,Western medicine group and TCM and Western medicine group are higher than model group and the differences are significant(P <0. 05 ,P <0. 01 ) ,while,at Oh,which are not significant within Western medicine group, normal group and TCM and Western medicine group ( P > 0. 05) ,even if which are significant between TCM group and TCM and Western medicine group or between model group and TCM and Western medicine group( P < 0. 05 ). At 48h, the differences of apoptosis ratios of PBLC are significant between Western medicine group and TCM and Western medicine group( P < 0. 05 ), and between TCM group and TCM and Western medicine group or between model group and TCM and Western medicine group which are significant, too( P < 0. 01 ). The ratios of bcl-2/bax mRNA of normal group,TCM group and TCM and Western medicine group are significantly lower than which of model group or Western medicine group ( P < 0. 05, P < 0. 05, P <0. 01 ,respectively) ,but there is no significant difference between which of model group and Western medicine group.Conclusion JQZR has adjustable effects on the apoptosis and expressions of bcl-2 and bax mRNA of peripheralblood lymphocyte in MRL/lpr Mice.
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Objective To investigate the effects of arsenic trioxide(ATO) on anti-dsDNA antibody and lymphocyte subsets proliferation in splenic cells of MRL/lpr mice.Methods MRL/lpr mice were divided into three groups: ATO group(0.4 mg/kg?d,ip),sodium chloride(NS) group(0.25 mL,ip),and cyclophosphamide(CTX) group(50 mg/kg?qw,ip).The control group consisted of 12 syngeneic normal C57/BL mice,which were sub-divided into ATO group(0.4 mg/kg?d,ip) and NS group(0.25 mL,ip).After two-month treatment,all mice were killed and their bodies and spleens were weighed.Anti-dsDNA antibody in serum were detected by ELISA.The percentage of different cell subsets was checked through flow cytometry.Results(1)The spleen index、serumlevel of anti-dsDNA antibody and the percentages of CD19+、CD3+、CD3+CD4+ lymphocytes in ATO group were much lower than those in NS group of MRL/lpr mice(P0.05). Conclusion Arsenic trioxide can inhibit the activation of T and B lymphocytes,increase the percentage of NK cell and reduce the serum level of auto-antibody.And it was of no effect in the normal mice.
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In our daily clinical practice, we have come across several patients suffering from a fluctuating sensorineural hearing loss of unknown origin. Such patients were sometimes treated with sucess by steroid administration. Some kinds of immune injury in the inner ear have been proposed as a possible pathogenesis. However, the minute mechanisms of immune injury in the inner ear and the way in which steroids improve the hearing loss remained obscure. We have previously reported that the MRL/MP-lpr/lpr(MRL/lpr) autoimmune strain of mice showed IgG deposition in the stria vascularis with elevated thresholds of auditory brainstem response. This strain of mice though to be a good model for studying immune mediated inner ear dysfunction. The purpose of this study was to evaluated the therapeutic efffects of prednisolone on the hearing impairment in MRL/lpr mice, morphologically and electrophysiologically.