| Objective:1.This research investigates the correlation between Henoch Schonlein purpura (HSP) in children and toll-like receptor pathway, further analyzes the pathogenesis of HSP and the possible targets of Xiao Dian Decoction, provides scientific basis for the clinical prevention and treatment of HSP by traditional Chinese medicine.2. To analvze the characteristics of HSP in children and observe the clinical effect of Xiao Dian Decoction in treating HSPMethods:1.A prospective before and after self control study is conducted,to observed the changes in immune parameters before and after Xiao Dian Decoction treatment, and compared with the healthy control group. Newly diagnosed 20 cases of HSP meeting the inclusion criteria in the outpatient and inpatient pediatric department of the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine from september 2009 to March 2011, are as treatment group;and 15 cases of healthy kids are as healthy control group. There are 12 males and 8 females in treatment group, and their average age is (7.1±2.0) years old. There are 9 males and 6 females in control group, and their average age is (6.9±1.1) years old. Children in treatment group take Xiao Dian Decoction(Herbs are provided by pharmacy and preparation room of the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine),is taken by the HSP children in the treatment group one dose per day, and one dose every two days after stable condition,4 weeks as a course of treatment. Children in healthy control group are not given any drug treatment. Fluorescent quantitative PCR is taken to detect the expression of TLR-2 mRNA, TLR-4 mRNA, NF-κB mRNA, IL-6mRNA in peripheral blood mononuclear cells and the value of ESR, C-reactive protein(CRP), C3, C4 in blood in treatment group before and after the treatment and those indicators are also detected from children in control group.2. A retrospective cohort study is conducted,360 cases of children with HSP are classified into Xiao Dian Decoction group(160 cases) and control group(200 cases) depending on whether taking Xiao Dian Decoction. Control group is classified into ontrol group 1 (80 cases) and control group 2(120 cases) depending on the main therapeutic principle. The warming and reinforcing herbs that can invigorating spleen and kidney are mainly taken in ontrol group 1, on the contrary, herbs eliminating pathogen are mainly taken in ontrol group2. The indicators such as the basic status (such as name, gender, incidence seasons, predisposing factors.), renal damage(such as hematuria, proteinuria, and their regression time),the total effect, the regression time of clinical symptoms, hospital stay and recurrent rate in one year, etc are observed in the three groups.Statistical analysis is performed after observation.Results:Clinical Research 11. Expression of TLR2mRNA, NF-κBmRNA and IL-6mRNA before and after HSP treatmentExpression of TLR2mRNA, NF-κBmRNA and IL-6mRNA in peripheral blood mononuclear of children with HSP are higher than healthy control group before treatment(P<0.01 or P<0.05). But the expression of TLR2mRNA, NF-κBmRNA and IL-6mRNA in peripheral blood monocytes decrease obviously after taking Xiao Dian Decoction for a course of treatment, there is significant difference compared with pre-treatment (P<0.01 or P<0.05).2. Correlation analysis between TLR2mRNA and NF-κBmRNA,IL-6 mRNA,ESR,CRP,C3,C4 before and after HSP treatmentSignificant correlation is found between expression of TLR2mRNA and NF-κBmRNA,IL-6 mRNA,ESR,CRP,C3,C4 before treatment in the monocytes of children with HSP (P<0.01).Compared with healthy control group, there is not significant difference in the expression of TLR2mRNA,NF-κBmRNA and IL-6 mRNA after taking Xiao Dian Decoction for a course of treatment (P>0. 05). There is not significant correlation between expression of TLR2mRNA in monocytes and ESR,C3,C4 before and after treatment (P>0.05). But There is significant correlation between expression of TLR2mRNA in monocytes and CRP before and after treatment(P<0.05 or P<0.01).3. Expression of TLR4mRNA and correlation analysis before and after HSP treatmentThere is not significant difference for TLR4mRNA expression in peripheral blood monocytes before and after treatment in children with HSP compared with healthy control group(P>0.05). Expression of TLR4mRNA decrease after taking Xiao Dian Decoction for a course of treatment in children with HSP, but there is not statistically significant (P>0.05). There is not significant correlation between expression of TLR4mRNA in monocytes and NF-κB, IL-6, ESR, CRP, C3, C4 before and after HSP treatment.Clinical Research 21. The clinical features of HSP in childrenComparison of gender distribution of 360 cases of HSP in children is that male to female ratio is 1.69. Incidence of male is higher than female.The age of disease occurrence is mainly distributed in school age and preschool. The largest incidence is occurred during school-age 4 to 12 years old, accounting for 85.2%.Total incidence of HSP in fall and winter seasons is more than that in spring and summer, Incidence of HSP in spring is close in summer. Infection factors account for about 48.1%in all incentives of disease, in which upper respiratory tract infection is most common, and gastrointestinal infection is second. Food allergy accounts for 15.6%, in which seafood is the most common. Oral drugs account for 13.1%. Other incentives account for 23.3%, including vaccination, mosquito insect bites, exposure to allergens and trauma etc.In terms of card type distribution and duration of HSP in children, Xiao Dian Decoction has no significant difference comparing with control group 1 and control group 2 (P>0.05)2. Overall clinical efficacy and symptoms improvement comparisonIn terms of overall clinical efficacy, the total effective rate of Xiao Dian Decoction is 85%, control group 1 is 73.8%, control group 2 is 75%. The total effective rate of Xiao Dian Decoction is better than that of control group 1 and control group 2(P<0.05), There is not significant different between control group 1 and control group 2 in the overall clinical efficacy comparison (P>0.05)In terms of symptoms improvement, The regression time of skin purpura in Xiao Dian Decoction is (5.42±3.51) days, and the regression time of abdominal pain in Xiao Dian Decoction is (4.36±1.61) days, which are significantly lower than control group 1 and control group 2 (P<0.05). But In terms of joint pain, Xiao Dian Decoction has no significant difference comparing with control group 1 and control group 2 (P>0.05)3. The function of prevention and treatment of Xiao Dian Decoction for renal damage caused by HSPOn analysis of renal damage appearing after treatment, the respective rate of occurrence of renal damage in 4 weeks,3 months and 1 year in Xiao Dian Decoction group respectively is 5.62%,9.38% and 5.63%, those in control group 1 respectively is 20.00%,15.00% and 18.75%, those in control group 2 respectively is 15.83%,13.33% and 12.50%. The number of renal damage after treatment in Xiao Dian Decoction group is significantly less than that in control group 1 and control group 2 (P<0.05). The number of renal damage in control group 2 is significantly less than that in control group 1, there is a significant difference between control group 1 and control group 2 (P<0.05)On comparison of effective rate of hematuria and proteinuria improvement, the totally effective rate of Xiao Dian Decoction group is highest, that is 81.7%, and the second is control group 2, the rate is 77.5%, control group 1 is lowest, that is 60.7%. The totallv effective rate of Xiao Dian Decoction is better than control group 1, there is a significant difference (P<0.05) The totally effective rate of control group 2 is better than control group 1 (P<0.05). The totally effective rate of Xiao Dian Decoction is higher than control group 1, but there is not significant different (P>0.05)On comparison of the regression time of hematuria and proteinuria, Xiao Dian Decoction group is shorter than control group 1 and control group 2, there are significant differences (P<0.01).The regression time of hematuria and proteinuria in control group 2 is shorter than control group 1 (P<0.05 or P<0.01)On comparison of the time renal damage occurs, The average time of renal damage occurrence in Xiao Dian Decoction group is (76±15) days, (35±13) days in control group 1, and (55±13) days in control group 2. The average time of renal damage occurrence in Xiao Dian Decoction group is significant later than control group 1 and control group 2 (P<0.05), and the time in control group 2 is later than control group 1, there is significant different (P<0.05)4. Hospital stay and recurrence rateThe proportion of hospital stay less than one week in Xiao Dian Decoction group account for 25.6%,1 to 2 weeks account for 41.3%,2 to 3 weeks account for 22%, more than 3 weeks account for 11.3%. The proportion of hospital stay less than one week in control group 1 account for 20%,1 to 2 weeks account for 26.3%,2 to 3 weeks account for 36.2%, more than 3 weeks account for 17.5%. The proportion of hospital stay less than one week in control group 2 account for 19.2%,1 to 2 weeks account for 26.7%,2 to 3 weeks account for 38.3%, more than 3 weeks account for 15.8%. The hospital stay in Xiao Dian Decoction group is less than control group 1 and control group 2 (P<0.01).There was no significant difference between control group 1 and control group 2 on hospital stay comparison.On comparison of recurrence rate, the recurrence rate in Xiao Dian Decoction group is 17%, the recurrence rate in control 1 is 45%, the recurrence rate in control 2 is 31.7%. The recurrence rate in Xiao Dian Decoction group is less than control group 1 and control group 2 (P<0.01). The recurrence rate in control group 2 is less than control group 1 (P<0.01)Conclusion1. The results of study indicate that the receptor pathways of TLR2mRNA, NF-κBmRNA and IL-6 mRNA are abnormally activated before the treatment of Xiao Dian Decoction, and the high expression of TLR2mRNA, NF-κBmRNA and IL-6 mRNA decrease to nornal level after the treatment of Xiao Dian Decoction, which is not significant different compared with healthy control group.The result indicates that the pathway of TLR2 to NF-κB may participate in the pathogenesis of HSP. TLR2 may participate HSP process by activating TLRs signal pathway and series of cascade of protein reactions to activate transcription factor NF-κB expression and release inflammatory factor IL-6.Xiao Dian Decoction may block or weaken some cytokine expression in NF-κB signal transduction pathway, downregulate inflammatory factor IL-6, effectively control inflammatory pathway and inflammatory mediators, to reach the effect of treating HSP. TLR4 expression may be unrelated to the pathogenesis of HSP. 2. TLR2 expression is significantly and positively correlated with CRP levels in the serum of children with HSP before and after treatment of Xiao Dian Decoction. So it is guessed that TLR2 expression reflects the changes of inflammatorv reaction and is taken as sensitive indicators of inflammation3. The incidence of HSP in boys was higher than that in girls. Onset age is mainly focused on school age and preschool. Autumn and winter are the most common incidence seasons.Infection factors account for main incentives of disease and other incentives are food allergy,oral drugs, vaccination, mosquito insect bites, exposure to allergens and trauma etc.4. Xiao Dian Decoction can effectively reduce the incidence of renal damage in children with HSP and delay the time of renal damage occurence. It has a better therapeutic effect in treating hematuria and proteinuria, Which can shorten the regression time of hematuria and proteinuria. Xiao Dian Decoction can also effectively reduce the hospital stay and the recurrence rate.It can improve the total effect and improve symptoms such as skin purpura and abdominal pain.5. In the acute stage of HSP, the incidence of renal damage in the children with HSP who mainly take warning and reinforcing herbs such as strengthening spleen and replenishing qi and reinforcing kidney herbs, is higher than that in the children with HSP who mainlv take Xiao Dian Decoction or eliminating-pathogen herbs such as dispelling wind and clearing heat herbs, at the same time, the regression time of hematuria and proteinuria in the former is significantly longer than that in the latter. The recurrence rate in the former is higher than that in the latter after treatment in one year.So.it is considered that warning and reinforcing method is cautious in the treatment of acute HSP in children. |
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