Background Fibrinogen(FIB)is often elevated in children with Henoch Schonlein purpuric nephritis(HSPN),but the correlation between FIB and renal lesions has been less studied.Objective To explore the correlation between FIB in children with HSPN and the International Study Group on Pediatric Kidney Disease(ISKDC)pathology grading and micropathological changes in parts of renal units,and to clarify whether FIB can assess the severity of renal injury in children with HSPN.Methods In total,922 children with HSPN who were hospitalized in the First Affiliated Hospital of Henan University of Chinese Medicine in the pediatric nephrology ward and underwent kidney biopsy at the same time from December 2017 to December 2022 were collected,and the clinical information,FIB and renal pathological information during renal biopsy were summarized,and based on the FIB level,the children were categorized into group A(low)<2.38 g/L,group B(standard)2.38-4.98 g/L,and group C(high)>4.98 g/L.The correlation between FIB and ISKDC pathological grades,glomerular mesangial hyperplasia ratio,the crescentic bodies ratio and the nature of the glomerular lesions from acute to chronic was investigated by Spearman rank correlation analysis,and the prediction of FIB on the micropathological changes of renal units was analyzed by the subject's work characteristic(ROC)curve.Results Among 922 children with HSPN who had undergone renal biopsy,the FIB was(3.48±1.01)g/L.113 cases in group A had a low FIB rate of 12.26%;734 cases in group B had a standardized FIB rate of 79.61%;and 75 cases in group C had a high FIB rate of 8.13%.The ISKDC pathology classification was type Ⅱa in 173 cases(18.76%),type Ⅱb in 29 cases(3.15%),466 cases(50.54%)of type Ⅲa,232 cases(25.16%)of type Ⅲb,and 22 cases(2.39%)of type Ⅳ and above(including 2 cases of type Ⅳa,18 cases of type Ⅳb,and 2 cases of type Ⅴ).The results of the Spearman's rank correlation analysis showed that the FIB and the grouping of the FIB of the children with HSPN were positively related to the renal pathology ISKDC grading(rs=0.146,P<0.001;rs=0.129,P<0.001).911(98.80%)of 922 children with HSPN were mesangial proliferative,and 655(71.04%)had crescentic hyperplasia.Spearman rank correlation analysis showed a weak positive correlation between FIB and FIB subgroups and the rate of mesangial hyperplasia(rs=0.092,P=0.005;rs=0.096,P=0.003),and a positive correlation with the rate of crescentic bodies(rs=0.132,P<0.001;rs=0.830,P=0.012).922 children with HSPN had glomerular acute lesions in 763 cases(82.75%),acute chronic lesions in 97 cases(10.52%),and chronic lesions in 62 cases(6.73%).In addition,FIB gradually increased with the nature of the glomerular lesions from acute to chronic(rs=0.145,P<0.001).At the same time,comparison of some renal biopsy indexes FIB in HSPN children showed statistically significant difference(P<0.05).The ROC curves showed that the FIB had the highest sensitivity for glomerulosclerosis(sensitivity=0.900,specificity=0.303),and the optimal cutoff value for FIB was 2.835 mg/L;the area under the ROC curve(AUC)of FIB for the positive prediction of tubulointerstitial fibrosis=0.623,and that of FIB for the reverse prediction of tubulointerstitial cellular granulomatous degeneration=0.641.Conclusion FIB can be used as a laboratory index reflecting the severity of renal pathological changes in patients with HSPN,can reflect the severity of renal pathological grading,is closely related to irreversible lesions according to renal microscopic indicators such as glomerular sclerosis and balloon adhesion,and can assist clinical diagnosis and treatment.

雷公藤是迄今为止免疫抑制作用最可靠的中药之一,被广泛应用于多种儿科疾病的治疗,但其不良反应特别是性腺毒性在很大程度上限制了在临床的使用.作为中医用药法则,"有故无殒"思想体现了"以毒攻毒"和"辨证论治"的中医治则和理念,为正确合理地认识雷公藤治疗作用与性腺毒性提供了思路,雷公藤对儿童性腺的影响既要权衡近期影响,也要考虑远期转归.大量临床研究及实验研究表明,雷公藤的性腺损害大多是"可逆"的,临床上通过采取合理的防治措施,雷公藤对儿童性腺的毒副作用是可以预测和预防的.

腹型过敏性紫癜是以腹部疼痛为主要表现的免疫紊乱性小血管炎性疾病,甚者可并发急腹症,严重危害患儿身心健康,目前认为其发病机制与"肠道微生态-免疫炎症"失调有关.糖皮质激素是西医推荐的首选用药.近年来中医药治疗本病疗效日渐显著,但具体机制不明.故本文从中医"阳明"为切入点,阐释肠道"微生态-免疫炎症"失衡与"阳明有余"二者之间的联系与内涵,为中医药靶向"微生态-免疫炎症"治疗和预防腹型过敏性紫癜提供新的研究思路.

目的 基于文献挖掘探讨中药减轻雷公藤雌性生殖毒性的规律分析,为临床合理用药、规避药物不良反应提供参考.方法 以"雷公藤、中草药、生殖"为主题,检索自1981年1月1日-2022年8月31日中国知网、万方、维普、中国生物医学文献数据库及PubMed、Cochrane Library、Embase数据库中相关研究文献,建立数据库,人工筛选文献,用Excel 2021数据透视表统计中药的药味、药性、归经和功效分类,用SPSS Modeler 18.0及SPSS Statistics 26.0软件进行可视化分析.结果 归纳总结符合纳入标准的43篇文献,共涉及84味减轻雷公藤雌性生殖毒性的中药,使用频率≥1％的有熟地黄、菟丝子、当归、枸杞子等28味中药,性味归经以甘、辛、苦3味,温、平、微温3性,肝、肾、脾3经占据前3,补阳药占21.88％,补血药占16.96％,补阴药占12.50％,补气药占10.49％,活血调经药占9.15％.药物关联分析得出21个常用药物组合.对频率≥1％的28味中药进行聚类分析,得出7个新处方.结论 雷公藤雌性生殖毒性的减毒用药规律中,熟地黄-菟丝子是高频药物中最常用的制约雷公藤雌性生殖毒性的药对.

Immunosuppressants are widely used in the treatment of rheumatic immune diseases, but most of them have toxic side effects, causing damage to the immune, digestive, reproductive and other systems, not only reducing patient compliance, but also seriously affecting disease prognosis. At present, Western medicine has no clear solution for the toxic side effects of immunosuppressants. The theory of traditional Chinese medicine（TCM） states that immunosuppressants such as glucocorticoids and cytotoxic drugs are mainly aggressive products. Long-term use of immunosuppressants can damage the lung, spleen and kidney, damage the vital qi of the body, and lead to deficiency symptoms occur. “Treating deficiency with three sources and two systems” is the great method developed by Wang Qishi, a doctor in the late Ming Dynasty, to treat deficiency and fatigue. After continuous enrichment and development in later generations, this has become a classic theory for treating consumption diseases. We studied the toxic side effects of immunosuppressants from the perspective of “treating deficiency with three sources and two systems”. We believe that the symptom of consumption caused by immunosuppressants should be treated from the “three sources” of lung, spleen and kidney, and the two types of syndromes of kidney yin deficiency and kidney yang deficiency should be treated from the “two systems” of lung and spleen. In clinical practice, we can determine the corresponding treatment principles according to different system’s injury syndromes, so as to provide a TCM scheme for safe clinical drug use and expand the theoretical system of toxicity reduction based on TCM.

Objective We aimed to explore the therapeutic mechanism of Qingre Zhixue Formula combined with tripterygium wilfordii multiglucoside in rats with Henoch-Sch?nlein purpura nephritis（HSPN）.Methods An HSPN rat model was established by intraperitoneal injection of ovalbumin and complete Freund’ s adjuvant. According to the random number table method, 54 rats with successful model were divided into the model group（n= 11）, the Qingre Zhixue Formula group（3. 17 mg/kg, n=11）, the tripterygium wilfordii multiglucoside group（ 4. 69 mg/kg, n= 11）, the combined group（3. 17 mg/kg Qingre Zhixue Formula + 4. 69 mg/kg tripterygium wilfordii multiglucoside, n= 11）, the hormone group（prednisone acetate 2. 34 mg/kg, n= 10）, in addition, nine rats in the blank group. Rats in the blank group and the model group were gavaged with the same amount of saline, and rats in the other groups were gavaged with corresponding drugs twice a day for 4 weeks. The urinary red blood cell count and the 24-hour urine protein quantification were determined by urine analyzer. The pathological changes of the mesangial area of rats were observed by transmission electron microscopy. The protein and m RNA expression levels of thioredoxin interacting protein（ TXNIP）, Nod-like receptor protein 3（NLRP3）, cysteine aspartic protease-1（Caspase-1） and interleukin-1β（IL-1β） in rat kidney tissue were detected by Western blotting and real-time PCR.Results Compared with the model group, the urinary red blood cell count, the 24-hour urine protein quantification, the protein expression levels of TXNIP, NLRP3 and Caspase-1 in the kidney tissues of rats in all treatment groups were reduced（P＜0. 05）. The glomerular thylakoid hyperplasia and basement membrane thickening of rats in each treatment group were improved, among which the most obvious improvement was observed in the combined group. The m RNA expression levels of TXNIP and NLRP3 in the kidney tissues of the rats in the combined group, the tripterygium wilfordii multiglucoside group and the hormone group were decreased（P＜ 0. 05）, the m RNA expression levels of IL-1β in the kidney tissues of the rats in the combined group and the hormone group were decreased（P＜0. 05）. Compared with the combined group, the urinary red blood cell count, the 24-hour urine protein quantification, the protein expression of TXNIP and NLRP3, and the m RNA expression levels of IL-1β in the kidney tissues of the rats in the remaining treatment groups were all increased（P＜0. 05）. The m RNA expression levels of TXNIP and NLRP3 in the kidney tissues of the rats in the tripterygium wilfordii multiglucoside group were increased（P＜0. 05）, the m RNA expression levels of NLRP3 in the kidney tissues of the rats in the Qingre Zhixue Formula group were increased（P＜0. 05）, the m RNA expression levels of TXNIP, NLRP3 and IL-1β were increased in the kidney tissues of the rats in the hormone group（P＜0. 05）.Conclusion Qingre Zhixue Formula combined with tripterygium wilfordii multiglucoside can effectively reduce the urinary red blood cell count and the 24-hour urine protein quantification in HSPN rats, and alleviate kidney injury, which may be related to the inhibition of the TXNIP/NLRP3/Caspase-1 inflammatory pathway.

Background: We determined the effects of Cuscutae semen (Cuscuta chinensis Lam. or Cuscuta australis R. Br.)–Radix rehmanniae praeparata (Rehjnannia glutinosa Libosch.) on the protein levels in testicular tissues of rats gavaged with tripterygium wilfordii multiglycosides (GTW) and elucidated the molecular mechanism underlying Cuscutae semen–Radix rehmanniae praeparata for relieving GTW-induced reproductive injury.Methods: A total of 21 male Sprague–Dawley rats were randomly divided into the control group, model group, and Cuscutae semen–Radix rehmanniae praeparata group based on their body weights. The control group was given 10 mLkg−1 of 0.9% normal saline by gavage daily. The model group (GTW group) was administered with 12 mg kg-1 GTW by gavage daily. Cuscutae semen–Radix rehmanniae praeparata group (the TSZSDH group) was administered with 1.56 gkg−1 of Cuscutae semen–Radix rehmanniae praeparata granules daily according to their model group dosing. The serum levels of luteinizing hormone, follicle-stimulating hormone, estradiol, and testosterone were measured after 12 weeks of continuous gavage, and the pathological lesion of testicular tissues was observed. Differentially expressed proteins were evaluated by quantitative proteomics and verified by western blotting (WB) and Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR).Results: Cuscutae semen–Radix rehmanniae praeparata can effectively relieve pathological lesions of GTW-induced testicular tissues. A total of 216 differentially expressed proteins were identified in the TSZSDH group and model group. High-throughput proteomics revealed that differentially expressed proteins are closely associated with the peroxisome proliferator-activated receptor (PPAR) signaling pathway, protein digestion and absorption, and protein glycan pathway in cancer. Cuscutae semen–Radix rehmanniae praeparata can significantly upregulate the protein expressions of Acsl1, Plin1, Dbil5, Plin4, Col12a1, Col1a1, Col5a3, Col1a2, Dcn, so as to play a protective role on testicular tissues. Acsl1, Plin1, and PPARγ on the PPAR signaling pathway were verified by WB and RT-qPCR experiments, which were found to be consistent with the results of proteomics analysis.Conclusion: Cuscutae semen and Radix rehmanniae praeparata may regulate the PPAR signaling pathway mediated Acsl1, Plin1 and PPARγ to reduce the testicular tissue damage of male rats caused by GTW.

Objective We aimed to（i） observe the effects of Shuangbu Pill（a compound prescription of prepared Rehmannia root and dodder seed） on reproductive damage induced by tripterygium glycosides in rats and（ii） explore its regulatory mechanism by metabolomic analysis.Methods Using the random number table method, 21 male 4-week-old Sprague-Dawley rats were randomly divided into the normal group, the tripterygium glycosides group（12.5 mg/kg）, and the Shuangbu Pill group（3.125 g/kg）（7 rats per group） and gavaged continuously for 12 weeks. The serum levels of testosterone（T）, follicle stimulating hormone（FSH）, luteinizing hormone（LH）, and estradiol（E 2 ） were measured by ELISA; sperm density and sperm motility were measured by an automatic sperm quality analyzer; histopathological changes of the testis and epididymis were observed by HE staining; ultrahigh-performance liquid chromatography coupled with tandem time-of-flight mass spectrometry combined with multivariate statistical method was used to detect and identify testicular tissue metabolites; and the Metabo Analyst platform was used for metabolic pathway analysis.Results Compared with the tripterygium glycosides group, the Shuangbu Pill could increase serum T levels（P＜0.01）, improve the sperm density and sperm motility（P＜0.01）, increase the number of spermatogenic cells in testicular tissue, reduce spermatogenic cell cavitation, and increase the number of epididymal sperm. According to our metabonomic analysis, after treatment with Shuangbu Pill, the levels of 19 differential metabolites related to reproductive damage caused by tripterygium glycosides could be significantly restored, which are mainly involved in glutathione metabolism and glycerophospholipid metabolism.Conclusion Shuangbu Pill can significantly reduce the reproductive damage caused by tripterygium glycosides, possibly through regulating glutathione metabolism and glycerophospholipid metabolism.

Objective To investigate the safety and efficacy of a traditional Chinese medicine（TCM） treatment of pediatric Henoch-Sch9nlein purpura nephritis（HSPN）（proteinuria below the nephrotic level）.Methods This study was a prospective multicenter stratified randomized controlled trial. In total, 316 children diagnosed with HSPN were divided into the Chinese medicine group（mild: n=132; severe: n=83） and the Western medicine group（mild: n=60; severe: n=41）. Patients in the Chinese medicine group were treated with tripterygium wilfordii multiglucoside + sulfotanshinone sodium injection+Qingre Zhixue Formula, the starting dose of tripterygium wilfordii multiglucoside for the Chinese medicine mild group was 1.5 mg/（kg·d）, while that for the Chinese medicine severe group was 2 mg/（kg·d）. Patients in the Western medicine mild group were treated with low-molecular-weight heparin calcium + benazepril + dipyridamole + a TCM simulator. In addition, patients in the Western medicine severe group received prednisone. The patients were treated for 12 weeks and followed up for 36 weeks. The urinary protein levels and urinary red blood cell（RBC） count were investigated in the 4th week and the 12th week. In addition, the recurrence rate at the end of 48 weeks of follow-up was calculated, and the incidence of adverse events at the end of 12 weeks of treatment was calculated.Results The urinary protein levels in the Chinese medicine group, the Chinese medicine mild group and the Chinese medicine severe group at the 4th week and the 12th week were significantly lower than in the Western medicine group, the Western medicine mild group and the Western medicine severe group（P＜0.01）. The urinary RBC counts in the Chinese medicine group, the Chinese medicine mild group and the Chinese medicine severe group at the 4th week and the 12th week were significantly lower than in the Western medicine group, the Western medicine mild group and the Western medicine severe group（P＜0.01）. No significant difference in recurrence rate was found between the Chinese medicine group and the Western medicine group, between the Chinese medicine mild group and the Western medicine mild group, or between the Chinese medicine severe group and the Western medicine severe group. The incidence of adverse events was lower in the Chinese medicine group than in the Western medicine group, and it was lower in the Chinese medicine severe group than in the Western medicine severe group（P＜0.01）, but there was no significant difference between the Chinese and Western medicine mild groups.Conclusion Chinese medicine alone can be used to reduce urinary protein levels and urinary RBC counts in both mild and severe HSPN. The effect of Chinese medicine on proteinuria was quicker than that of Western medicine, and the incidence of adverse events was significantly lower in the Chinese medicine group than in the Western medicine group. The stepwise Chinese medicine scheme, which is mainly based on tripterygium wilfordii multiglucoside combined with Qingre Zhixue Formula, shows an excellent curative effect and fewer adverse events, indicating it is worthy of clinical promotion.

Immunoglobulin A (IgA) vasculitis (IgAV), also known as Henoch-Schönlein purpura, is the most common form of childhood vasculitis. It is characterized by cutaneous hemorrhage, resulting from red blood cell leakage into the skin or mucosae, possibly caused by damage to small blood vessels. These acute symptoms usually disappear without treatment. Endothelial cells are distributed on the inner surfaces of blood vessels and lymphatic vessels, and have important functions in metabolism and endocrine function, as well as being the primary targets of external stimuli and endogenous immune activity. Injury to endothelial cells is a feature of IgA vasculitis. Endothelial cell damage may be related to the deposition of immune complexes, the activation of complement, inflammatory factors, and chemokines, oxidative stress, hemodynamics, and coagulation factors. Both epigenetic mechanisms and genetic diversity provide a genetic background for endothelial cell injury. Here, research on the role of endothelial cells in allergic IgA vasculitis is reviewed.

肾小球新月体病变是紫癜性肾炎(HSPN)重要的病理表现之一,随着HSPN发病率的升高,减少或延缓肾损伤的发生已成为防治HSPN的共识."久病入络"理念来自叶天士《临证指南医案》,强调了病久入络,由气至血的传变规律,阐明了络脉损伤、络脉瘀阻等病理变化.HSPN属于"络病"范畴,病变部位在于肾络(肾小球毛细血管),肾络纤细迂曲,盘根错杂,血行缓慢而易瘀滞.伏邪触动、正气不足、脏腑本虚可致体内精微物质代谢失常、脏腑结构功能改变,为瘀血的产生创造了条件,成为了肾小球新月体病变的基础.病程的长短、病情的轻重均可致瘀,病程长、病情重者则瘀更甚,病情发展也越快,治疗上需把握"络通则瘀去"的原则,肾络畅行,血不瘀滞,则可延缓疾病进展.

目的:探讨清热止血方联合雷公藤多苷治疗紫癜性肾炎患儿的临床疗效,为临床应用提供依据.方法:收集紫癜性肾炎患儿45例,使用中央随机系统按1:2分为对照组15例,观察组30例,对照组给予贝那普利联合双嘧达莫治疗,观察组给予清热止血方联合雷公藤多苷治疗,疗程12周,观察2组患儿治疗4、8、12周的临床疗效及不良事件发生率,Elisa法检测血清可溶性血管内皮生长因子受体(soluble vascular endothelial growth factor receptor,sFlt)-1、血管性血友病因子(von Willebrand factor,vWF)的变化.结果:治疗4周观察组降低蛋白尿疗效高于对照组,差异有统计学意义(P<0.05);2组治疗8、12周降低尿蛋白疗效比较差异无统计学意义(P>0.05).观察组与对照组在治疗12周时血清sFlt-1、vWF水平均较治疗前显著下降(P<0.05);观察组在治疗4周时,血清sFlt-1表达水平较对照组明显下降(P<0.05),2组患儿治疗期间均有轻度不良事件发生,组间比较差异无统计学意义(P>0.05).结论:清热止血方联合雷公藤多苷能有效降低紫癜性肾炎患儿尿蛋白量,下调血清sFlt-1、vWF水平,与对照组比较起效更快且无明显不良反应.

This study systematically searched CNKI and Web of Science(WoS) for the research papers on the toxicity of Tripterygium wilfordii included from database inception to August 31, 2021, and visually displayed the authors, research institutions, keywords, and other contents using bibliometrics and CiteSpace 5.8.3. Furthermore, the current situation and research progress on T. wilfordii safety were also analyzed based on information extraction to find the research hotspot, evolution path, and development trend, and to provide references for future research. A total of 1 876 Chinese papers and 243 English papers were included in the study. The analysis of authors showed that WANG Qi and ZHANG Luyong had the most publications in Chinese and English papers, respectively. According to the analysis of research institutions, National Institutes for Food and Drug Control and China Pharmaceutical University possessed the largest number of Chinese and English papers, respectively, but there was less cooperation between them. The analysis of keywords in Chinese and English papers showed that the research contents of the safety of T. wilfordii mainly focused on clinical monitoring, mechanism, dosage form improvement, quality standard, component analysis, monomer research, efficiency and toxicity reduction, etc. Metabonomics, tripterine, and the underlying mechanism of toxicity were the research hotspots in the future. At present, the research on the toxicity of T. wilfordii is still under development. It is necessary to highlight the in-depth research and strengthen the inter-group and inter-region cooperation of authors or institutions to provide references for the research on the toxicity of T. wilfordii.

目的:搜集整理多年来中医药治疗紫癜性肾炎的中英文文献,以了解演变过程及研究热点,为研究本病提供参考.方法:检索中国知网及Web of Science自建库至2021年9月28日已发表的中医药治疗紫癜性肾炎的国内外相关文献,运用CiteSpace 5.8.R3软件对研究作者、机构及关键词等内容进行可视化图谱显示,并结合文献查阅对中医药治疗紫癜性肾炎的研究热点及发展趋势进行分析.结果:经过筛选,最终纳入中文文献1263篇,英文文献448篇.张君、SUZUKI分别是中英文发文量最多的研究作者;辽宁中医药大学、福岛县立医科大学分别是中英文发文量最多的研究机构;研究显示机构之间缺少良好的交流合作;对中医药治疗紫癜性肾炎的中、英文文献里的关键词分析,主要表现在发病人群、临床表现、肾脏病理分型、治疗方案、结局及预后,中文文献更加强调中医药的应用,例如儿童发病,症见皮肤紫癜、血尿,治则为活血化瘀、清热解毒,用药为雷公藤等,英文文献更注重实验室检查,例如凝血功能、牛津分型、结局及预后等.结论:图谱直观展示了自1976年至2021年9月28日中医药治疗紫癜性肾炎近45年的研究情况,明确了当前中医药治疗紫癜性肾炎领域的研究现状及趋势,但是仍存在一些研究不足,需更进一步深入研究并且加强作者及机构间的合作,为今后研究紫癜性肾炎提供可靠依据.

Tripterygium glycoside tablet (TGT) is a common clinically used and effective non-steroidal immunosuppressant. However, its reproductive toxicity limits its application in pediatric immune diseases, warranting the study of the molecular mechanism behind its reproductive toxicity. In the present study, 4-week-old male Sprague Dawley (SD) rats were provided TGT through continuous gavage with a clinically equivalent dose of 12 mg/kg for 12 weeks. The reproductive toxicity of TGT was recorded, and its toxicity mechanism was verified through experimental validation and proteomics analyses. Our results demonstrated that TGT could significantly reduce the testosterone level in the serum as well as the concentration and survival rate of sperms. Pathological sections of the testis revealed that TGT could reduce spermatocytes at different levels and make the convoluted meridians vacuolated. Based on tandem mass tag (TMT)-labeled quantitative rats testicular tissue proteomics, 34 differential proteins were screened, involving protein digestion and absorption, PPAR signaling pathway, PI3K-Akt, and other pathways, among which PI3K-Akt plays an important role in the study of reproductive injury. Western blotting results revealed that TGT could significantly downregulate the Col1A1, Col1A2, p-PI3K, and p-Akt expressions and inhibit the expression of proteins related to the PI3K-Akt signaling pathway. In summary, the clinically equivalent dose of TGT induced reproductive toxicity of 4-week-old male SD rats, possibly in relation to the inhibition of the PI3K-Akt pathway expression.

目的:探讨清热止血方联合雷公藤多苷对紫瘢性肾炎(HSPN)核转录因子-κB(NF-κB)信号通路的影响及作用机制.方法:72只SD大鼠随机分为空白组12只、造模组60只,采用复合瘀热模型法制备HSPN的动物模型,将成功造模大鼠随机分为模型组、清热组(清热止血方3.17mg/kg)、雷公藤组(雷公藤多苷片4.69mg/kg)、联合组(清热止血方3.17 mg/kg+雷公藤多苷片4.69 mg/kg)、激素组(醋酸泼尼松2.34 mg/kg),分别给予相应药物,2次/d,持续4周.采用酶标法检测尿红细胞计数、尿蛋白定量及肝肾功能;采用免疫荧光法检测肾脏组织中IgA沉积;采用透射电镜观察大鼠肾小球系膜区的病变情况;采用Western blot及qRT-PCR检测大鼠肾组织IKK β、IκBα、P65、P50蛋白及mRNA的表达水平.结果:与空白组比较,模型组尿红细胞计数和尿蛋白定量显著升高(P＜0.05);与模型组比较,各药物组尿红细胞计数和尿蛋白定量显著下降(P＜0.05).与空白组比较,模型组可见肾小球系膜区较强的IgA表达,肾小球系膜增生,系膜区电子致密物沉积,基底膜弥漫性增宽,内皮细胞肿胀,足突部分融合;与模型组比较,各药物组肾小球系膜区IgA表达减弱,肾小球系膜增生、基底膜增厚及内皮细胞肿胀情况减轻,仍可见少量足突融合.与空白组比较,模型组肾组织中IKK β、P65、P50蛋白及mRNA的表达显著升高(P＜0.05),IκBα蛋白及mRNA的表达显著降低(P＜0.05);与模型组比较,各药物组肾组织中IKKβ、P65、P50蛋白及mRNA的表达显著降低(P＜0.05),IκB α蛋白及mRNA的表达显著升高(P＜0.05).结论:清热止血方联合雷公藤多苷可降低HSPN大鼠的血尿及蛋白尿水平,其机制可能是通过抑制NF-κB信号通路的激活,减少炎症反应.

为探讨紫癜性肾炎(Henoch-Sch?nlein purpura nephritis,HSPN)患儿系膜区C3沉积与肾脏病理及免疫指标的相关性,纳入2015年1月至2017年12月河南中医药大学第一附属医院儿科肾脏病区行肾活检的HSPN患儿249例.采用微量免疫比浊法测定患儿血清IgA、IgM、IgG、C3、C4水平;采用流式细胞术测定CD3+、CD4+、CD8+T细胞水平;采用免疫荧光法对肾组织中IgA、IgM、IgG、C3和纤维蛋白(fibrin,Fib)沉积进行评价.结果显示,根据C3沉积强度,将患儿分为A组135例(-～±,54.2％)、B组83例(+,33.3％)、C组31例(++,12.4％).在249例患儿中,肾脏病理I级1例(0.4％)、Ⅱa级41 例(16.5％)、Ⅱb级18例(7.2％)、Ⅲa级100例(40.2％)、Ⅲb级79例(31.70％)、Ⅳ级9例(3.6％)、V级1例(0.4％).C3沉积强度与肾脏病理分级呈正相关(r=0.127,P=0.045).血清补体C3水平与肾小球系膜区C3沉积程度呈负相关(r=-0.210,P=0.001).IgA、IgM、C4、IgG水平的组间比较,差异无统计学意义(P＞0.05);CD4+/CD8+T与C3沉积程度组间比较(A组与B组、A组与C组),差异有统计学意义(P＜0.05),且大部分患儿伴有CD4+/CD8+T下降.血清CD3+、CD4+、CD8+T细胞水平组间比较,差异无统计学意义(P＞0.05).这提示HSPN患儿肾脏损伤程度与肾小球系膜区C3沉积有关,C3沉积程度越高,肾脏损伤越严重,相应的血清补体C3水平也越低,反映出机体的免疫功能低下.

目的 观察紫癜性肾炎(HSPN)患儿血清可溶性血管内皮生长因子受体-1(sFlt-1)、血管性血友病因子(vWF)水平变化,并探讨其临床意义.方法 HSPN患儿45例(HSPN组),过敏性紫癜(HSP)患儿15例(HSP组),同期健康体检儿童15例(对照组),采用酶联免疫吸附法检测各组血清sFlt-1、vWF,Pearson相关分析法分析HSPN组患儿血清sFlt-1与vWF水平的相关性.结果 与对照组比较,HSPN组及HSP组血清sFlt-1、vWF水平升高(P均<0.05);与HSP组比较,HSPN组血清sFlt-1、vWF水平升高(P均<0.05).HSPN组血清sFlt-1与vWF水平无相关性(r=-0.24,P=0.180).结论 HSPN患儿血清sFlt-1、vWF水平升高,两者可能参与HSP早期肾脏损伤.

目的 观察雷公藤多苷片联合清热止血方对紫癜性肾炎患者的临床疗效.方法 168例患者随机分为对照组(55例)和观察组(113例),对照组给予强的松联合贝那普利、双嘧达莫,观察组给予雷公藤多苷片联合清热止血方,疗程12周.检测临床疗效、T细胞亚群(CD3、CD4、CD8、CD4/CD8)、免疫球蛋白(IgA、IgG、IgM)、补体(C3、C4)、不良反应发生率变化.结果 4周末,观察组减少蛋白尿疗效优于对照组(P＜0.05);12周末,观察组减少尿红细胞疗效优于对照组(P＜0.05).治疗后,2组CD3、CD4、CD4/CD8升高(P＜0.05),CD8、IgA降低(P＜0.05),以观察组更明显(P＜0.05).2组不良反应发生率比较,差异无统计学意义(P＞0.05).结论 雷公藤多苷片联合清热止血方能安全有效地降低紫癜性肾炎患者蛋白尿水平,改善免疫状态.

目的 运用数据挖掘方法分析丁樱教授治疗紫癜性肾炎的用药、配伍规律及其治疗思想.方法 搜集其在2017年5月-2019年5月间门诊治疗紫癜性肾炎的医案处方作为研究对象,运用软件Excel 2013进行药物频数统计,SPSS Modeler 14.1的Apriori建模进行关联规则分析及SPSS Statistics 23.0进行系统聚类分析.结果 在纳入标准的152首方剂中,涉及中药161味,累积次数1614次,频数排列前五的药物依次为地黄、当归、连翘、牡丹皮、芡实等,用药类别以清热凉血、清热解毒以及补血药为主.经关联规则分析得到常用药对关联规则17条,3味药关联规则28条,4味药关联规则6条.经系统聚类分析归为6类.结论 丁樱教授治疗紫癜性肾炎主要以清热凉血,活血化瘀为法,结合病程及临床症状,辅以益气温肾养血治疗,故基于数据挖掘对丁樱教授用药规律探索,有助于指导中医治疗紫癜性肾炎的临床实践.