| Henoch-Schonlein Purpura(HSP)is an inflammatory disease of small blood vessels mediated by the deposition of IgA immune complexes,and it is common in children.Its etiology is not completely clear,and Henoch-Schonlein Purpuric nephritis is a common complication.It belongs to the categories of "blood syndrome","grape disease" and "macular eruption" of Chinese medicine.Qingzi granules is a preparation in the hospital of Beijing Children's Hospital.It is composed of Chinese materia medica such as Indigo Naturalis,Lithospermum,Dryopteris crassirhizoma,Salvia miltiorrhiza,Angelicae dahurica,Gypsum rubrum,Clematis root,Artemisia Capillaris,etc.This compound has the effect of removing wind and detoxification,cooling blood and removing spots and make definite effect on HSP.Qingzi Granules are prepared by modifying the formulation of Qingzi Mixture.In this experiment,based on the efficacy of Qingzi Granules and the possible pathogenesis of Henoch-Schonlein Purpura,we observed the effect of Qingzi Granule on kidney damage of HSP and researched its mechanism of action,by establishing ovalbumin(OVA)induced HSP rat model and a mouse model of HSP induced by gliadin.1 The effects of Qingzi Granules on rats with Henoch-Schonlein Purpura induced by OVA.Objective To observe the effects of Qingzi Granules on serum immunoglobulin A(IgA),circulating immunocomplex(CIC),serum amyloid A(SAA),interleukin-6(IL-6),endothelin(ET-1),nitric oxide(NO)levels,and the effects on skin and renal histopathology in rats with HSP induced by OVA.Methods SPF grade SD rats were randomly divided into normal group,model group,low-dose group(4.58 g·kg-1),middle-dose group(9.16 g·kg-1)and high-dose group(18.32 g·kg-1),dexamethasone group(0.55 mg·kg-1),and Luding tablet group(12.05 mg·kg-1).The rat model of HSP was established by means of integrated traditional Chinese and western medicine.The rats were intragastrically administrated with 1.2 ml of decoction of pepper,dried ginger and piper longum(1:1:1),twice a day for 21 days.Then,except the normal group,other groups rats were intraperitoneally injected the suspension consisted of OVA,Al(OH)3,LPS and Evans blue for 1 ml each one on the 22nd day,and the normal group was intraperitoneally injected with an equal dose of physiological saline.On the same day,each administration group was administered with the drug solution at the above dosage,and the normal group and the model group were administered with the same amount of vehicle for 7 days.An allergic reaction was induced by smearing administration of 1 ml saline containing OVA,Al(OH)3 and LPS within 10 min after the second injection on the 29th day.Blood is taken within 30 min,IgA,CIC,SAA,IL-6,ET-1 and NO levels in serum were detected by ELISA.Pathological observations of kidneys and skins were performed by HE staining.RESULTS Compared with the normal group,the levels of serum IgA,CIC,SAA,IL-6,ET-1 and NO were increased,and renal tissue pathological damage was obvious(P<0.05 or P<0.01).Qingzi Granules can reduce the levels of serum IgA,CIC,SAA,IL-6,ET-1 and NO in rats with HSP induced by OVA,and alleviate renal pathological damage(P<0.05 or P<0.01).Conclusion Qingzi Granules can reduce the level of serum IgA,CIC,SAA,IL-6,ET-1 and NO,and improve pathological injury of renal tissue in rats with HSP induced by OVA.2 The effects of Qingzi Granules on mice with Henoch-Schonlein Purpura induced by Gliadin.Objective To observe the effects of Qingzi Granules on the levels of advanced oxidized protein products(AOPPs),circulating immunocomplex(CIC),creatinine(Cr),urea nitrogen(BUN)in serum,and the effects on immunoglobulin A(IgA)deposition and abnormal glycosylation of IgA1 of skin and kidney,and the effects on complement C3,complement C4 and TGF-?1 expression and histopathology in gliadin-induced HSP mice.Methods SPF grade KM mice were randomly divided into normal group,model group,low-dose group(4.11 g·kg-1),middle-dose group(8.22 g·kg-1),and high-dose group(16.44 g·kg-1),the dexamethasone group(0.63 mg·kg-1),and the Luding tablet group(12.54 mg·kg-1).A mouse model of HSP was established by means of using the oral gliadin method.In addition to the normal group,the remaining groups were injected with Indian ink at 0.4 mg/10 g through the tail vein for 3 weeks,once a week.The normal group was given an equal dose of physiological saline.After 3 weeks,the model mice were intragastrically administrated with 6 mmol/L HCl acidified water which dissolved with 0.1%gliadin at 0.5 ml each mouse for 14 consecutive weeks,once every other day.The normal group treated with the same solvent.On the last 3 days,1 mg gliadin was added to PBS solution(pH=7.4)which was acidified by 5 mmol/L HCl,and injected with 0.2ml through the tail vein,once a day for 3 consecutive days.The mice in the normal group were injected with the same amount of PBS solution in the tail vein.From the 15th week,each administration group was intragastrically administered with the drug solution at the above dosage once a day for 3 consecutive weeks.The normal group and the model group were intragastrically administered with the same amount of vehicle.Blood was collected from each group,and serum levels of AOPPs,CIC,BUN and Cr were measured by ELISA.Skin and kidney were taken,immunofluorescence was used to detect kidney and skin IgA deposition.Abnormal glycosylation of IgA1 in skin and kidney were observed by PAS staining.Immunofluorescence was used to detect mice's skin and renal complement C3,complement C4,and TGF-?1 expression,and histopathological changes were observed by HE staining.Results Compared with the normal group,the serum levels of AOPPs,CIC,BUN,and Cr in the model group were increased(P<0.05 or P<0.01),and the expression of complement C3 and TGF-?1 at skin in the model group were increased(P<0.05 or P<0.01),and the expression of kidney IgA and complement C4 were increased(P<0.05 or P<0.01).Abnormal glycosylation of IgA1 occurred in the skin and kidney,and the pathological damage of kidney tissue was obvious.Qingzi granules can reduce the serum AOPPs,CIC,BUN,Cr levels in HSP mice induced by gliadin,and decreased the expression of skin complement C3 and TGF-?1,and reduce the expression of kidney IgA,complement C3,complement C4 and TGF-?1 in HSP mice,and alleviate the pathological damage of the kidney,and reduce the abnormal glycosylation of skin and kidney IgA1.Conclusion Qingzi granules can alleviate the renal damage of HSP mice caused by gliadin,and this effect is related to reducing the level of AOPPs,the deposition of IgA,CIC,and abnormal glycosylation of IgA1,and down-regulating the expression of complement protein and TGF-?1.In summary,Qingzi granules have a protective effect on kidney damage in a HP animal models,and reducing IgA and CIC deposition,AOPPs levels,and down-regulating the expression of complement protein and TGF-? may be its main action pathway. |
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