刘光珍教授临床运用凉血散血法治疗慢性肾脏病的经验

正慢性肾脏病起病隐匿,病程长,病理表现复杂多样,常见病理表现有肾小球球性硬化、节段性毛细血管塌陷或狭窄,血管襻挤压、闭塞,球囊黏连,系膜基质增多,基底膜增厚,肾小管灶状萎缩,肾间质灶状淋巴细胞和单核细胞浸润及纤维化等[1]。导师刘光珍在临床诊疗过程中发现,中医肾络瘀阻、肾微癥瘕证候表现与肾脏病理诊断为肾小球硬化、肾间质纤维化等患者的临床表现甚为相似。导师在临床慢性肾脏病诊疗过程中衷中参西,注重中西医结合,辨证地认识中医肾病与现代医学肾脏     

复合感染法联合5/6肾切除IgAN肾小球硬化模型的病理研究

目的 通过复合感染法联合5/6肾切除的方法来建立IgAN肾小球硬化模型建立,为进一步研究lgAN的进展提供理论依据.方法 将24只SD雄性大鼠分为假手术组、5/6肾切除组、复合感染组、复合感染合5/6肾切除组,观察大鼠肾组织免疫荧光沉积、光镜观察肾结构变化及电镜观察肾脏超微结构变化.结果 复合感染法联合5/6肾切除的方法大鼠肾组织免疫荧光病理中肾小球系膜区尤以IgA免疫沉积物为主,光镜可见肾小球硬化和肾小管间质纤维化的形成,电镜观察肾小球系膜区可见大量的电子致密物的沉积并伴区域性的肾小球硬化和肾小管间质大量纤维化的改变.结论 复合感染法联合5/6肾切除缩短了IgAN肾小球硬化模型制作时间.     

中医综合措施对肾衰竭大鼠病理组织的影响

目的：通过对5/6肾切除肾衰竭模型大鼠药物干预,观察肾脏病理组织,进一步验证中药综合措施对肾衰竭的疗效。方法：采用5/6肾切除肾衰竭模型,一次性摘除右肾并切除左肾的2/3,随机分为病理组、通脉组、结肠组、综合组及正常对照组,治疗4周后,切除肾脏光镜及电镜病理检查。进行组间比较。结果：中药综合措施可改善模型大鼠的一般状态,能减轻肾脏病理损害突出表现在抑制系膜细胞与系膜基质增殖,减少肾小球萎缩硬化的发生,改善肾间质纤维化,减轻肾小管损害。结论：中药综合措施可有效地延缓肾衰竭大鼠的恶化进程,优于其他单一药物组。     

转化生长因子β与糖尿病肾病的发病机理

肾脏病变是最常见和最严重的糖尿病慢性并发症之一。糖尿病肾病的主要病理变化包括肾小球和肾小管的肥大、肾小球及肾小管基底膜增厚、肾小球系膜区细胞外基质堆积以及肾小管间质的硬化,其发生机制尚不十分明确。近年来转化生长因子β(transforminggrowth factor-β,TGF-β)的介导作用已越来越受到人们的重视,我们对TGF-β与糖尿病肾病发病的关系作一综述。     

全反式维甲酸延缓糖尿病肾脏纤维化进展的实验研究

目的：探讨全反式维甲酸对延缓糖尿病大鼠肾脏纤维化的保护作用。方法：随机选择雄性SD大鼠分为空白对照组（NC）与造模组,制作糖尿病模型分为模型组（DM）与维甲酸治疗组（DM＋atRA）。于模型成型后分别于第8、12周观察各组大鼠24h尿蛋白（Ualb）,内生肌酐清除率（Ccr）,肾重／体重。肾脏病理及电镜观察肾小球基底膜厚度,免疫组织化学方法观察肾组织Ⅳ、Ⅲ型胶原表达。结果：维甲酸组肾重／体重、Ualb、Ccr较同时期模型组下降（P＜0．05）,且12周大鼠肾组织细胞外基质（ECM）重要成分ColⅣ表达（5．75±0．41）、ColⅢ表达（4．98±1．37）与模型组比较显著减少（P＜0．01）。病理观察维甲酸组与模型组比较肾小球系膜细胞和内皮细胞增生减轻,足突融合改善,系膜基质增生缓解,基底膜厚度变薄,减轻了肾脏病理损害。结论：全反式维甲酸能减轻糖尿病大鼠早期肾脏病理损伤,减少细胞外胶原基质积聚,延缓肾脏纤维化。     

骨碎补总黄酮对系膜增生性肾炎大鼠血清白细胞介素-6的影响

目的：观察骨碎补总黄酮对系膜增生性肾小球肾炎大鼠血IL-6及尿蛋白的影响。方法：利用免疫法制备大鼠系膜增生性肾小球肾炎模型,将大鼠分为骨碎补总黄酮组（治疗组）、病理对照组（模型组）、正常对照组,检测各组24h尿蛋白、血清IL-6,并观察肾脏病理改变。结果：模型组大鼠肾脏系膜细胞明显增生,与正常对照组比较24h尿蛋白定量及血清IL-6明显升高（P＜0．05）;治疗组大鼠肾脏系膜细胞增生减轻,24h尿蛋白、血IL-6均明显低于模型组（P＜0．05）。结论：骨碎补总黄酮能降低系膜增生性肾小球肾炎大鼠尿蛋白,降低血清IL-6水平,减轻系膜细胞增生和细胞外基质增加,延缓或减轻肾组织损伤,保护肾功能。     

滋肾活血法干预实验性DN模型大鼠的实验研究

目的:观察滋肾活血法(活血降糖胶囊)对实验性糖尿病肾病(diabetic nephropathy,DN)模型大鼠的肾脏保护作用。方法:取SD雄性大鼠,予部分肾切除合并单次小剂量腹腔注射STZ,同时给予隔日高脂饲料建造DN动物模型,筛选DN成模大鼠,随机分成模型(DNM)组、中药(HX)组、西药(IR)组并随机设正常对照(NC)组,分别予中西药物干预;8周后处死大鼠,检测尿蛋白、血糖、肾功能、血脂,电镜及光镜观测肾脏超微病理结构变化,测量肾小球截面积(MGA)、细胞外基质截面积(MMA)、肾小球基底膜厚度(GBM),计算细胞外基质截面积/肾小球截面积(MMA/MGA)比值及肾小球硬化指数(GSI)。结果:HX组大鼠24h尿蛋白定量、GSI、GBM、MMA/MGA比值较DNM组均明显降低(P<0.01),光镜、电镜示病理损害较DNM组改善。HX组血脂较IR组、DNM组降低(P<0.05或P<0.01)。结论:滋肾活血中药复方活血降糖胶囊可减轻实验性DN模型大鼠蛋白尿及肾脏损害,改善脂质代谢,发挥肾脏保护作用。     

三七总皂苷对5/6肾切除大鼠肾脏皮质细胞外基质积聚的影响

目的：观察三七总皂苷（PNS）对5/6肾切除大鼠肾皮质细胞外基质（ECM）积聚的影响,并探讨其肾脏保护机制。方法：将45只Wistar大鼠按体重随机取8只为正常对照组,余用5/6肾切除法建立慢性肾衰竭（CRF）动物模型。将造模成功后的大鼠随机分为模型组、百令胶囊组（简称对照组）、PNS低剂量组（低剂量组）、PNS高剂量组（高剂量组）,分别给与相应浓度和剂量的药物,实验期间测定大鼠的尿蛋白、肾功能,治疗12周后观察其肾脏病理改变,用半定量方法计算肾小球硬化指数（GSI）和肾小管损伤指数,免疫组化法检测肾小球Ⅳ型胶原（ColⅣ）、纤连蛋白（FN）和肾皮质基质金属蛋白（MMP-2）和金属蛋白酶组织抑制物（TIMP-2）蛋白表达。结果：PNS能明显减少CRF大鼠尿蛋白的排出（P〈0.05）,有一定改善肾功能的作用;PNS能减轻肾脏病理损害,减轻肾小球硬化、肾小管损伤程度;PNS能下调TIMP-2蛋白表达,增加MMP-2活性,抑制了FN、ColⅣ在肾组织的表达（P〈0.01）,减轻ECM积聚。结论：PNS可能通过减少5/6肾切除大鼠尿蛋白的排出,增加肾脏MMP-2活性,降低TIMP-2表达,增加ECM降解,减轻肾小球硬化,从而起到治疗作用。     

益肾泻浊方对慢性肾衰竭大鼠内皮素表达的影响

多种肾脏疾病 ,尽管其病因、病理类型不同 ,但最终结局均为肾小球硬化 ,肾小管 -间质纤维化。内皮素在ＣＲＦ发病中起重要作用 ,它可改变肾血液动力学、血粘度、促进肾小球系膜细胞 (ＭＣ)增殖。益肾泻浊方是我们在临床上用于治疗慢性肾衰竭的有效方剂 ,经临床验证有效率达85 .6 %。该方能改善肾功能 ,降低尿蛋白 ,抑制ＭＣ、成纤维细胞 (ＦＣ)增殖 ,减少ＥＣＭ积聚。本实验在此基础上 ,研究益肾泻浊方对 5 /6肾切除ＣＲＦ大鼠ＥＴ - 1表达的影响 ,从而进一步探讨其延缓慢性肾衰竭进展的作用机理。资料与方法1　实验动物及分组　清洁级雄性…     

巨噬细胞在大鼠糖尿病肾病发病机制中的作用

目的:研究巨噬细胞在糖尿病大鼠肾脏的浸润情况并与肾损害程度作相关性分析,以探讨巨噬细胞在糖尿病肾病发病机制中的作用.方法:健康雄性Wistar系大鼠分为单肾切除对照组和实验组,分别于糖尿病成模后2周、4周、8周处死各组1/3数量大鼠,检测肾重、内生肌酐清除率、24 h尿微量白蛋白排泄量等指标,光镜、电镜观察肾脏病理组织学改变,免疫组化分别检测肾脏CD68、CD3标记的巨噬细胞和淋巴细胞的浸润情况并与肾损害程度作相关性分析.结果:实验组大鼠随着病程的延长,肾重增加,内生肌酐清除率增高,并出现进行性微量白蛋白尿,与对照组有统计学差异.8周时实验组大鼠肾脏肾小球体积增大,毛细血管基底膜增厚,平均约890nm,系膜细胞增生,系膜外基质增多,肾小球系膜区面积占肾小球面积的比值较对照组明显增多.免疫组化显示,8周时糖尿病组大鼠肾小球区域可见多量的CD68阳性的巨噬细胞浸润,约为(7.29±2.14)cells/gcs,而对照组几乎未检测到,约为(0.4±0.55)cells/gcs,二者有统计学差异(P＜0.05).两组均未检测到CD3阳性的淋巴细胞.肾脏浸润的巨噬细胞与肾损害程度(用24 h尿微量白蛋白排泄量表示)存在明显的正相关(P＜0.05).结论:在糖尿病肾病早期肾脏有巨噬细胞积聚,并与肾损害程度呈正相关,提示巨噬细胞有可能在糖尿病肾病发病机制中起促进作用.     

糖尿病肾病大鼠模型瘀血阻络证的确认

目的：通过观察血瘀证客观指标和病理形态学的改变,以及化瘀通络中药的干预作用,从正、反两个角度判断糖尿病肾病大鼠模型有无瘀血阻络的病理改变.方法：将雄性SD大鼠随机分为空白对照组（C组）、高糖高脂对照组（H组）和模型制备组,以高糖高脂饲料联合腹腔注射STZ制备模型,并随机分为模型组（M组）和化瘀通络中药组（Z组）.Z组大鼠给予化瘀通络中药灌胃治疗16周,其余各组灌以相应体积饮用水.观察注射STZ后16周末各组大鼠临床指标、肾脏病理和血脂、血流变的改变情况.结果：M组大鼠于腹腔注射STZ后3 d,血糖升高,并逐渐出现多饮、多食、多尿、体重减轻及大量蛋白尿的表现;肾脏病理改变为肾小球体积增大,基底膜增厚,系膜增生,肾小囊腔缩小;肾体重比值、血脂、全血黏度、血浆黏度、全血低切还原黏度和红细胞压积均显著高于C组（P〈0.01）,红细胞变形指数显著低于C组、H组（P〈0.01）,Z组各指标均较M组差异有统计学意义（P〈0.05）.结论：糖尿病肾病大鼠模型存在明显的血瘀证和肾组织病理形态学改变;化瘀通络中药干预后,模型大鼠上述指标得到明显改善.可见,无论直接观察还是以方（效）测证,均可说明该方法制备的糖尿病肾病大鼠模型存在明显的瘀血阻络证候.     

“下法”治疗腰椎间盘突出症的临床研究

目的:探讨中医“下法”在临床治疗腰椎间盘突出症中的运用.方法:132例腰椎间盘突出症的患者按照中医辨证分型,其中气滞血瘀型65例,风寒湿型48例,肾虚型19例,分别用中医的“寒下”中的大黄牡丹汤、“温下”中的大黄附子汤、“润下”中的麻子仁丸治疗.结果:132例患者中优良104例,占78.6%;可19例,占14.4%;差9例,占6.9%.结论:中医“下法”能有效地改善患者下肢功能,缓解腰腿疼痛,对腰椎间盘突出症有较好的治疗作用.     

骨形成蛋白7和转化生长因子β1在不同病理类型IgA肾病的变化

目的 观察转化生长因子β1（TGF-β1）和骨形成蛋白7（BMP-7）在不同病理类型IgA肾病的变化,并探讨其意义。方法 89例IgA肾病患者分成3组：A组为47例轻度系膜增生性IgA肾病;B组为29例中重度系膜增生性IgA肾病;C组为13例增生硬化或硬化性IgA肾病。检测患者的血压、尿蛋白量（24 h）、Scr和Ccr。免疫组化和ELISA方法测定患者肾组织冰冻切片及其血、尿中TGF-β1和BMP-7水平。计算患者病理切片硬化肾小球数、新月体数和间质纤维化面积百分比。结果 随着IgA肾病患者肾小球病变的加重,肾小管萎缩和肾间质纤维化增多,其血压、尿蛋白量（24 h）、Scr逐渐增加,除B、C两组间尿蛋白量（24 h）无显著差异外,其余各组间差异均有统计学意义（P＜0．05）。与A组比较,B组肾组织及血、尿TGF-β1明显增多,C组显著降低（P＜0．01）。肾组织冰冻切片及血、尿BMP-7随着肾脏病变的加重,水平逐渐下降（P＜0．01）;而且与Ccr呈正相关;与血压、Scr、尿蛋白量（24 h）、硬化肾小球数、新月体数、肾间质纤维化面积呈负相关。结论 TGF-β1在IgA肾病系膜增生严重时明显增加,肾脏广泛纤维化时明显降低,可能参与了IgA肾病肾间质纤维化的发生。BMP-7随肾脏病变的加重而明显降低,可能导致其抗肾纤维化作用减弱。     

Inflammatory lymphangiogenesis in a rat transplant model of interstitial fibrosis and tubular atrophy

We have previously reported de novo lymphangiogenesis in human renal allograft nephrectomy specimens that exhibited interstitial fibrosis and tubular atrophy (IFTA). This study examined whether a similar pathology developed in an experimental model of renal transplantation in the rat. Renal transplants were carried out in rats comprising both isografts (Lewis kidneys → Lewis rats) and allografts (Fisher kidneys → Lewis rats). Animals were immunosuppressed in the immediate postoperative period and sacrificed at 12 months. Experimental readouts included lymphatic vessel number and location, inflammatory cell infiltration, interstitial fibrosis, renal function, blood pressure and proteinuria. Rat allografts demonstrated the characteristic features of IFTA with increased macrophage and T cell infiltration and scattered B cells aggregates. Rat allografts exhibited impaired renal function and proteinuria. Although there was no difference in the number of perivascular lymphatic vessels, there was a striking 18-fold increase in the number of interstitial lymphatic vessels in renal allografts. Furthermore, the lymphatic vessel number correlated with the extent of interstitial fibrosis. This rat allograft model of IFTA demonstrates a marked increase in the number of interstitial lymphatic vessels and mirrors previous work in failing human renal allografts.     

基于中医瘀血理论探讨骨质疏松症中医发病机制认识及治疗进展

随着我国社会人口老龄化日渐加剧,骨质疏松症(osteoporosis,OP)患病率亦显著增加,已成为我国三大老年慢性疾病之一.高发病率、严重并发症及昂贵的医疗费用等使其成为全球关注的公共健康问题.近年来以中医理论为指导的相关研究不断深入,显示出中医药治疗OP的独特优势.既往研究大多以"肾主骨生髓"理论进行研究,瘀血理论...     

Advanced IgA nephropathy with impaired renal function benefits from losartan treatment in rats

Abstract

Background: Treatment with angiotensin receptor blockers (ARBs) is successful in mitigating IgA nephropathy (IgAN), independent of blood pressure changes, but the therapeutic role of ARB in advanced IgAN with impaired renal function is to be ascertained. The present study was performed to investigate the effect of losartan on advanced IgAN induced by staphylococcal enterotoxin B (SEB) combined with 5/6 nephrectomy in rats. Methods: Fifty-four male SD rats were randomly divided into three group: Rats in the model group were treated with SEB plus 5/6 nephrectomy, and those in the losartan group were gavaged with losartan (33.3?mg?kg^?1?d^?1) besides the treatment with SEB plus 5/6 nephrectomy. The urine and blood biochemical changes of rats were tested. IgA, IgG, IgM and C3 depositions were studied dynamically with immunofluorescence. The renal tissue structures were observed under light microscopy. The expressions of TGF-β1, FN, alpha-SMA and FGF-1 in rat renal tissues were determined with immunohistochemical methods and real-time PCR. Results: At 12 weeks, rats with SEB treatment plus 5/6 nephrectomy showed gradually increased urinary red blood cell (URBC) with a gradual elevation of the 24?h urinary protein, serum BUN and Scr, but losartan treatment lowered the levels of 24?h urinary protein, serum BUN and Scr. A large number of IgA depositions in the mesangial area, glomerulosclerosis and tubulointerstitial fibrosis were found in the model group, and the losartan group showed relieved injury. The expressions of TGF-β1, FN, alpha-SMA and FGF-1 were significantly elevated in the model. Losartan lessened their expressions. Conclusion: Losartan treatment can delay the progression of advanced IgA nephropathy with impaired renal function.     

Captopril reduces interstitial renal fibrosis and preserves more normal renal tubules in neonatal dogs with partial urethral obstruction: a preliminary study

PURPOSE: Chronic renal damage due to tubulointerstitial fibrosis is one of several complications of posterior urethral valves in a significant number of children. As activation of the renin-angiotensin system plays an important role in this injury, we conducted this study to investigate whether administration of captopril reduced renal fibrosis in an experimental model using partial urethral obstruction (PUO) in neonatal dogs. MATERIAL AND METHODS: Experimental PUO was induced in all pups. These animals were then divided into two groups: in the first group (experimental), captopril 35 mg/kg/day, dissolved in drinking water, was administered for 6 weeks. The second group (positive control) did not receive any treatment. After 6 weeks all dogs underwent left nephrectomy. Volume fraction and absolute volume of the histological kidney parameters, i.e., normal glomerulus, normal tubule, vessels, degenerated glomerulus, degenerated tubule, fibrous tissue, were estimated using modern unbiased stereological methods. RESULTS: The absolute volume of interstitial fibrosis was lower in the experimental group (PUO with captopril treatment) (approximately 73%; p < 0.008) in comparison with positive control animals (PUO with no treatment). The mean absolute volume of normal tubules in the experimental group was more than the positive control group (approximately 33%, p < 0.008). The mean absolute volume of normal and degenerated glomerulus, vessels and degenerated tubule did not show a significant difference between the two groups. CONCLUSION: Administration of captopril decreases interstitial renal fibrosis and preserves renal tubules in neonatal dogs with PUO.     

Spontaneous rupture of the renal pelvis in a female patient with defect of the uterus and hypoplasia of the vagina: a case report

A 17-year-old woman consulted our clinic with the complaint of gross hematuria and lower abdominal pain. Blood examination showed severe anemia and renal failure. Emergent hemodialysis and blood transfusion were performed. CT scanning revealed left retroperitoneal hematoma, right severe hydronephrosis and loss of uterus shadow. Under diagnosis of left renal rupture, left nephrectomy and removal of retroperitoneal hematoma were performed. The area of rupture in the left renal pelvis was identified on its posterior wall. Postoperatively renal function did not improve and periodic hemodialysis has been done.     

Expanded experience with laparoscopic nephrectomy and autotransplantation for severe ureteral injury

PURPOSE: Complex injuries of the upper ureter with significant loss of length are difficult to manage. Traditional options include nephrectomy, bowel interposition and autotransplantation. The advent of laparoscopic donor nephrectomy has created a new option when preservation of functioning renal parenchyma is desirable. We update our experience with severe iatrogenic ureteral injuries requiring laparoscopic nephrectomy and autotransplantation. MATERIALS AND METHODS: Seven patients with severe ureteral injuries were referred for definitive management. In all cases preoperative evaluation demonstrated comparable split renal function and anatomy not amenable to routine reconstruction. Transperitoneal laparoscopic nephrectomy and autotransplantation to the ipsilateral pelvis were attempted. RESULTS: Of the patients 5 had a history of nephrolithiasis with intervention resulting in the ureteral injury and 5 underwent prior endoscopic or open management of the defects. All cases were associated with dense perinephric and perihilar fibrosis. Operative and warm ischemic times averaged 508 and 5 minutes, respectively. After ex vivo graft preparation, ureteral and vessel length and quality were adequate for transplantation in 6 cases. In the other patient the renal pelvis was not amenable for reconstruction. Urinary drainage consisted of ureteroneocystostomy in 2 cases and ipsilateral ureteroureterostomy in 4. There were no intraoperative complications and all grafts functioned immediately. Hospitalization averaged 6.4 days. At a mean followup of 17 months imaging studies demonstrated functioning renal autographs with a mean decrease in serum creatinine of 5%. CONCLUSIONS: Laparoscopic nephrectomy in conjunction with autotransplantation is a viable option for severe proximal ureteral loss. Acceptable perioperative morbidity and excellent graft function were obtained in all cases when the kidney was transplanted. Close cooperation with a transplant team is crucial to coordinate graft harvest, ensure appropriate organ preparation and select the optimal urinary anastomosis.