Diabetic nephropathy (DN) is one of the most serious chronic microvascular abnormalities of diabetes mellitus and the major cause of uremia. Accumulating evidence has confirmed that fibrosis is a significant pathological feature that contributes to the development of chronic kidney disease in DN. However, the exact mechanism of renal fibrosis in DN is still unclear, which greatly hinders the treatment of DN. Chinese herbal medicine (CHM) has shown efficacy and safety in ameliorating inflammation and albuminuria in diabetic patients. In this review, we outline the underlying mechanisms of renal fibrosis in DN, including oxidative stress (OS) generation and OS-elicited ASK1-p38/JNK activation. Also, we briefly summarize the current status of CHM treating DN by improving renal fibrosis. The treatment of DN by inhibiting ASK1 activation to alleviate renal fibrosis in DN with CHM will promote the discovery of novel therapeutic targets for DN and provide a beneficial therapeutic method for DN.

目的:通过观察治疗前后实验室指标的变化,以探讨白通汤对慢性肾脏病3期脾肾阳虚患者疗效的可能作用机制.方法:将2019年5月至2021年4月收治的90名符合慢性肾脏病3期脾肾阳虚证的患者,随机分为对照组和治疗组,对照组接受西医基础治疗,治疗组在西医基础治疗上加用白通汤.治疗组及对照组均连续治疗4周,在治疗前后分别对比两组中医证候积分、转化生长因子-β1(TGF-β1)、人附睾蛋白4(HE4)、超氧化物歧化酶(SOD)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6).结果:治疗组治疗后中医证候积分较对照组低,治疗组治疗总有效率(88.89％)比对照组(66.67％)高,比较差异有统计学意义(P＜0.05).治疗后治疗组SOD水平比对照组高,血清IL-6、TNF-α、TGF-β1、HE4水平比对照组低,差异具有统计学意义(P＜0.05).结论:白通汤对慢性肾脏病3期脾肾阳虚证患者的临床疗效确切,具有减轻患者症状,延缓疾病进展的作用,其可能的作用机制与提高抗氧化能力、减轻微炎症状态、延缓肾间质纤维化进展有关.

詹继红为贵州省省级名中医,全国优秀中医临床人才,善于治疗肾系疾病,如慢性肾衰竭、肾病综合征、紫癜性肾炎、急慢性肾盂肾炎、狼疮肾等.精通中医四大经典及各家学说,并常教导学生学习中医不能忘根.在中医淋证方面有着其特有的见解与临床经验,基于《黄帝内经》中上古天真论,詹继红认为淋证在不同年龄阶段淋证的病因病机及治疗要点各有不相同,强调治疗淋证要讲究因人而异,同病异治.现就该思想做以下总结.

IgA肾病在我国的肾脏疾病中所占比重逐年增高,是导致终末期肾病的重要原因之一,其临床表现多种多样,病理类型复杂多变,实验室检查尚缺乏特异性诊断,激素及免疫抑制剂治疗虽然可以减轻患者病证,但是用药时间长,且激素毒副作用明显.贵州中医药大学第一附属医院肾脏病内科主任詹继红教授总结多年治疗脾肾两虚型IgA肾病临床经验,具有明显的临床疗效,值得临床推广.

Background: In clinical practice, Chinese herbal medicine (CHM) purportedly has beneficial therapeutic effects for chronic kidney disease (CKD), which include delaying disease progression and dialysis initiation. However, there is a lack of high-quality evidence-based results to support this. Therefore, this study aimed to evaluate the efficacy of CHM combined with Western medicine in the treatment of stage 5 CKD.Methods: This was a prospective nonrandomized controlled study. Stage 5 CKD (nondialysis) patients were recruited form 29 AAA class hospitals across China from July 2014 to April 2019. According to doctors’ advice and the patients’ wishes, patients were assigned to the CHM group (Western medicine + CHM) and the non-CHM group (Western medicine). Patient demographic data, primary disease, blood pressure, Chinese and Western medical drugs, clinical test results, and time of dialysis initiation were collected during follow-up.Results: A total of 908 patients were recruited in this study, and 814 patients were finally included for further analysis, including 747 patients in the CHM group and 67 patients in the non-CHM group. 482 patients in the CHM group and 52 patients in the non-CHM group initiated dialysis. The median time of initiating dialysis was 9 (7.90, 10.10) and 3 (0.98,5.02) months in the CHM group and non-CHM group, respectively. The multivariate Cox regression analysis showed that patients in the CHM group had a significantly lower risk of dialysis [adjusted hazard ratio (aHR): 0.38; 95% confidence interval (CI): 0.28, 0.53] compared to those in the non-CHM group. After 1:2 matching, the outcomes of 160 patients were analyzed. The multivariate Cox regression analysis showed that patients in the CHM group had a significantly lower risk of dialysis (aHR: 0.32; 95% CI: 0.21, 0.48) compared to patients in the non-CHM group. Also, the Kaplan-Meier analysis demonstrated that the cumulative incidence of dialysis in the CHM group was significantly lower than that in the non-CHM group (log-rank test, P<0.001) before and after matching.Conclusions: This study suggest that the combination of CHM and Western medicine could effectively reduce the incidence of dialysis and delay the time of dialysis initiation in stage 5 CKD patients.

Chinese herbal medicine (CHM) might have benefits in patients with non-diabetic chronic kidney disease (CKD), but there is a lack of high-quality evidence, especially in CKD4. This study aimed to assess the efficacy and safety of Bupi Yishen Formula (BYF) vs. losartan in patients with non-diabetic CKD4. This trial was a multicenter, double-blind, double-dummy, randomized controlled trial that was carried out from 11-08-2011 to 07-20-2015. Patients were assigned (1:1) to receive either BYF or losartan for 48 weeks. The primary outcome was the change in the slope of the estimated glomerular filtration rate (eGFR) over 48 weeks. The secondary outcomes were the composite of end-stage kidney disease, death, doubling of serum creatinine, stroke, and cardiovascular events. A total of 567 patients were randomized to BYF (n = 283) or losartan (n = 284); of these, 549 (97%) patients were included in the final analysis. The BYF group had a slower renal function decline particularly prior to 12 weeks over the 48-week duration (between-group mean difference of eGFR slopes: −2.25 ml/min/1.73 m2/year, 95% confidence interval [CI]: −4.03,−0.47), and a lower risk of composite outcome of death from any cause, doubling of serum creatinine level, end-stage kidney disease (ESKD), stroke, or cardiovascular events (adjusted hazard ratio = 0.61, 95%CI: 0.44,0.85). No significant between-group differences were observed in the incidence of adverse events. We conclude that BYF might have renoprotective effects among non-diabetic patients with CKD4 in the first 12 weeks and over 48 weeks, but longer follow-up is required to evaluate the long-term effects. Clinical Trial Registration: http://www.chictr.org.cn, identifier ChiCTR-TRC-10001518.

目的:分析益气温阳补肾汤治疗肾病综合征的临床疗效.方法:选2020年4月～2021年4月98例肾病综合征患者进行研究,采用随机数表法分为观察组(49例,益气温阳补肾汤)与对照组(49例,醋酸泼尼松龙片).对比临床疗效、生化指标水平.结果:观察组患者临床疗效显著高于对照组,(P<0.05);观察组患者ALB水平显著高于对照组,24hPro水平显著低于对照组,(P<0.05).结论:益气温阳补肾汤可有效提高对患者临床疗效,改善患者生化指标水平,值得广泛推广.

目的:探讨六味地黄汤联合黄葵胶囊治疗早期高血压肾病患者脉压及蛋白尿临床疗效.方法:选取贵州省中医院2018年10月—2019年8月收治的80例辨证为阴虚夹湿型高血压肾病患者,按照随机数字表法分为对照组和观察组,每组40例.对照组患者用厄贝沙坦治疗,并嘱患者低盐、低脂、低蛋白饮食,观察组患者除以上基础治疗外另加六味地黄汤联合黄葵胶囊进行治疗,比较两组患者治疗前后血压波动、尿β2-微球蛋白、尿微量白蛋白水平及临床疗效.结果:观察组患者经过治疗后在血压等指标的恢复程度优于对照组,差异有统计学意义(P<0.05);观察组中医证候疗效明显优于对照组(P<0.05);观察组尿β2-微球蛋白、尿微量白蛋白水平均明显低于对照组,差异有统计学意义(P<0.05);观察组不良反应发生率低于对照组,但无统计学差异(P>0.05).结论:在常规西医治疗基础上采用黄葵胶囊联合六味地黄汤治疗阴虚夹湿型高血压肾病可有效降低患者血压水平,降低尿β2-微球蛋白、尿微量白蛋白水平,安全且无副作用.

紫癜性肾炎是由于毛细血管的变态反应导致的肾脏炎性病变,其发病人群多见于小儿以及青少年,发病时多伴有蛋白尿以及镜下血尿.詹继红教授认为该病核心问题为肾虚不固兼加瘀、热、风、湿为标,治法以补肾健脾益气为主,清热贯穿其中,注重风、血、湿的治疗.

目的 介绍詹师在诊治肾虚腰痛中的特色心悟.方法 分析肾虚腰痛的病因病机,总结詹师的临床经验,并附上医案两例,以供参考.结果 特色如下:①填精补肾,温中健脾;②补益肾精,气血调和,强壮腰府.结论 詹师诊治肾虚腰痛疾病,从八纲辨证、脏腑辨证入手,同时重视气血的升降浮沉,施治临床,疗效显著.

目的 探究刺梨冻干粉治疗CKD3期患者血脂异常的临床疗效及安全性.方法 将40例符合标准的患者用随机数字分组法分为两组,治疗组和对照组.在试验期间所有基础治疗不变(控制血压、血糖,纠正机体代谢紊乱、CKD常规治疗等).在常规治疗基础上,对照组口服氯沙坦钾片,50 mg/次,1次/日;治疗组在常规治疗的基础上加服刺梨冻干粉,5g/次,1次/日,餐后吞服.两组均观察12周,观察两组治疗效果,第0、12周抽取患者外周静脉血检测血脂相关指标(胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)等,第0、6、12周观察血肌酐(CREA)、丙氨酰氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、肌酸激酶、肌红蛋白等安全性指标.结果 治疗12周后两组血脂治疗疗效比较具有统计学意义(P>0.05),实验期间2组安全性指标均未见明显异常,未见患者有其他不良症状.结论 刺梨冻干粉对CKD3期脂代谢紊乱患者血脂治疗具有较好的临床疗效与安全性.

目的:探究凉血散瘀汤联合替米沙坦治疗肾虚血瘀型IgA肾病疗效及对肾脏纤维化的影响.方法:将我院自2018年9月至2019年9月所收录的54例肾虚血瘀型lgA肾病患者为研究对象,按随机数表进行分组分为对照组和观察组,每组27例,对照组患者给予替米沙坦片口服,观察组患者使用凉血散瘀汤联合替米沙坦的方式进行治疗,对比两组患者的各项数据对比以及不良反应的发生情况.结果:观察组患者在尿蛋白定量、尿红细胞计数均低于对照组(P<0.05);观察组的肾脏纤维化指标均优于对照组患者(P<0.05),两组患者数据对比具有统计学意义.结论:凉血散瘀汤联合替米沙坦对治疗肾虚血瘀型IgA肾病的效果中具有良好的使用价值.

目的 探讨苗药刺梨延缓单侧输尿管、结扎术(UUO)模型大鼠肾间质纤维化的作用机制.方法 将50只SPF级雄性SD大鼠,适应性喂养1 w后,随机分为假手术组和手术组;手术组行UUO,假手术组只行输尿管分离,但不结扎.术后第2天,手术组随机分为模型组、SIRT1激动剂组、刺梨中剂量组、氯沙坦钾组,每组10只.各组于分组当天参照马氏定理设定干预剂量.氯沙坦组给予氯沙坦10 mg/(kg·d),浓度为20％;刺梨中剂量给予刺梨冻干粉3 g/(kg·d),浓度为3％;SIRT1激动剂组给予白藜芦醇25 mg/d.模型组和假手术组均同时给予同等容积无菌生理盐水灌胃.实验大鼠均每天干预1次,连续干预14 d后处死大鼠.取大鼠肾组织做苏木素-伊红(HE)、Masson染色以观察其病理变化;免疫组织化学法测定Western印迹检测肾组织转化生长因子(TGF)-β1、TGF-βⅠ型受体(TGF-βRⅠ)、Smad2、Smad3、Smad7的表达;用RT-PCR技术检测TGF-β1 mRNA、TGF-βRⅠmRNA、Smads2、Smad3、Smad7 mRNA的表达.结果 与假手术组比较,模型组病理损伤程度显著增加,丙二醛(MDA)含量增加、超氧化物歧化酶(SOD)含量降低(P<0.01),TGF-β1、TGF-βRⅠ的表达水平明显增加(P<0.05).与模型组比较各治疗组病理损伤减轻,TGF-β1、TGF-βRⅠ表达减少,Smda2、Smad3的表达降低,Smda7表达增加(均P<0.05).刺梨中剂量组与SIRT1激动剂组比较差异无显著性(P>0.05).结论 刺梨冻干粉与SIRT1激动剂(白藜芦醇)均可减轻单侧输尿管结扎肾间质纤维化大鼠的肾组织脂质过氧化物的产生,同时能增加抗氧化酶的含量,保护受损肾小管上皮细胞,有效改善肾脏纤维化病变.其机制可能与其富含维生素C、SOD、刺梨黄酮等多种抗氧化成分,激活体内SIRT1,从而活化Smda7以下调TGF-β1、TGF-βRⅠ及Smda2、Smad3的表达有关.

目的 探讨肾茶黄酮预防急性肾缺血模型大鼠再灌注损伤的作用及其机制.方法 48只SD大鼠编号并根据随机数表分为研究组(n=24)和对照组(n=24).两组均行右肾切除和左肾动脉夹闭1 h以制造肾缺血再灌注模型.研究组在再灌注24 h开始腹腔注射0.1 g/ml肾茶黄酮配比液2 ml,2次/d.对照组同期腹腔注射等量0.9％生理盐水.再灌注24 h、48 h、72 h、96 h分别随机处死大鼠6只.检测比较再灌注不同时间后的肾组织Bax和Bcl-2蛋白阳性表达率、血清超氧化物歧化酶(SOD)活力、丙二醛(MDA)等氧化应激指标水平、血清肌酐(SCr)、肾损伤分子(KIM)-1等肾功能指标水平.并分析研究组血清肾功能指标水平与其肾组织Bax和Bcl-2蛋白阳性表达率、血清氧化应激指标水平的关系.结果 两组灌注24 h组各指标比较无明显差异(P>0.05).与对照组比较,研究组灌注48 h、72 h、96 h的肾组织Bax蛋白阳性表达率、血清SOD活力水平显著升高而同期肾组织Bcl-2蛋白阳性表达率、血清MDA水平及血清SCr、KIM-1等肾功能指标水平显著降低(P<0.05).研究组血清SCr、KIM-1水平与其肾组织Bax蛋白阳性表达率呈负相关(r=-0.792,-0.831,P<0.05),与其肾组织Bcl-2蛋白阳性表达率则呈正相关(r=0.805,0.879,P<0.05).研究组血清SCr、KIM-1水平与其血清SOD活力水平呈负相关(r=-0.811,-0.842,P<0.05),与其血清MDA水平则呈正相关(r=0.863,0.795,P<0.05).结论 肾茶黄酮可有效预防急性肾缺血模型大鼠再灌注损伤,而调控Bax和Bcl-2表达及降低氧化应激反应可能为其预防急性肾缺血再灌注损伤作用机制.

Fibrosis is involved in the pathogenesis of kidney diseases. We previously discovered that Rosa roxburghii fruit (Cili) possesses antifibrosis property in chronic renal disease, but the mechanisms are unknown. We hypothesized that Cili might prevent fibrosis development through mediating TGF-β/Smads signaling, which is known to be involved in renal fibrosis. This study aimed to confirm the effects of freeze-dried Cili powder in a rat model of unilateral ureteral obstruction (UUO) and examine TGF-β/Smads signaling. Rats were randomized to (n=12/group): sham operation, UUO, UUO with losartan, UUO with moderate Cili dose (3 g/kg/d), and UUO with high Cili dose (6 g/kg/d). The rats were sacrificed after 14 days of treatment. Collagen deposition was tested using Masson’s staining. TGF-β/Smads signaling was examined by qRT-PCR, western blot, and immunohistochemistry. Rats in the UUO group showed excessive deposition of collagen in kidney interstitium, accompanied with high levels of renal 8-hydroxy-2′-deoxyguanosine, renal malondialdehyde, blood urea nitrogen (BUN), serum creatinine (Scr), and proteinuria (all P<0.05). Cili powder efficiently alleviated the pathological changes and oxidative stress in the kidneys of UUO rats, and decreased BUN, Scr and proteinuria (all P<0.05). Cili powder also inhibited the upregulation of TGFB1, TGFBR1, TGFBR2, SMAD2, and SMAD3 and reversed the downregulation of SMAD7 in obstructed kidneys (mRNA and protein) (all P<0.05). In summary, the results suggest that Cili freeze-dried powder effectively prevents renal fibrosis and impairment in UUO rats, which is associated with the inhibition of oxidative stress and TGF-β1/Smads signaling.

目的 研究苗药刺梨对于脾肾气虚型CKD3期患者成纤维细胞生长因子23(FGF23)-Klotho轴的干预与安全性.方法 将62例符合纳入标准的患者用随机数字表法分为治疗组和对照组.所有受试者在试验期间,均予西医基础治疗(控制高血压、纠正电解质代谢紊乱等).治疗组:刺梨冻干粉,5g/次,1次/d,餐后吞服.对照组:氯沙坦钾片,50 mg/次,1次/d.2组均观察24周,第0、24周行中医症状分级量化表评分,并采集外周静脉血栓测血清中FGF23、Klotho蛋白水平,第0、2、8、16、24周观察血肌酐(CREA)、丙氨酰氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、血钾(K+)等安全性指标.结果 治疗组总有效率为83.87％,对照组总有效率为38.7％,2组比较差异有统计学意义(P＜0.05).治疗后2组FGF23均较治疗前下降(P＜0.05),且治疗组的下降幅度优于对照组(P＜0.05);治疗后2组Klotho蛋白均较治疗前升高(P＜0.05),且治疗组升高幅度优于对照组(P＜0.05);治疗期间2组安全性指标均未见明显异常,未见不良反应.结论 苗药刺梨对脾肾气虚型CKD3期患者具有较好的临床疗效与安全性,其机制可能为调控FGF23-Klotho轴的表达所致.

目的 观察白通汤干预治疗脾肾阳虚型CKD4期慢性肾炎患者蛋白尿的临床疗效与安全性.方法 将60例符合纳入标准的患者用随机数字表法分为治疗组和对照组.每组各30例.对照组采用西医慢性肾脏病一体化治疗,治疗组在对照组治疗的基础上,加服白通汤治疗.4周为1个疗程.并观察尿蛋白定量、血肌酐的变化.结果 治疗组总有效率为83.33％,对照组总有效率为40％,2组疗效比较差异有统计学意义(P＜0.01);2组治疗前后尿蛋白定量比较有统计学意义(P＜0.01).结论 白通汤干预治疗脾肾阳虚型CKD4期具有较好的临床疗效和安全性.

目的 观察超声引导联合介入技术在血液透析患者动静脉内瘘狭窄中的临床应用效果.方法 60例血液透析患者作为研究对象,随机分成对照组与观察组,各30例.对照组应用介入技术(经皮腔内血管成形术)治疗,观察组应用超声引导联合介入技术治疗,对比两组穿刺时间、手术时间、穿刺并发症发生率、术后瘘口血流量等指标.结果 观察组穿刺时间、手术时间分别为(5.19±1.93)、(61.05±13.56)min,均短于对照组的(8.41±5.65)、(71.62±17.83)min,差异具有统计学意义(P<0.05).观察组穿刺并发症发生率为3.33％,低于对照组的20.00％,差异具有统计学意义(P<0.05).观察组内瘘口血流量为(538.02±32.98)ml/min,高于对照组的(518.36±36.01)ml/min,差异具有统计学意义(t=2.2052,P<0.05).结论 超声引导联合介入技术在血液透析患者动静脉内瘘狭窄中的临床应用效果较好,可以缩短穿刺和手术时间,减少并发症的发生,值得临床推广应用.

慢性肾脏病(CKD)目前已成为全球威胁人类健康的公共卫生问题,我国成年人群中CKD的患病率为10.8％,CKD的知晓率仅为12.5％.而CKD进行性发展最终会进入终末期肾病.因此,加强对CKD的防治,已成为不可忽视的公共卫生问题之一.故早期发现、早期诊断、早期治疗、早期人为干预,延缓CKD进程就显得尤其重要.导师经过临床观察发现焦虑状态与CKD进展有关联性,有研究指出,CKD患者较正常人群更易发生焦虑;因此,对情绪因素的治疗应该成为CKD治疗的一个重要的组成部分.笔者通过探索性临床研究,初步观察精神、情绪因素(焦虑状态)在CKD慢性进程中的作用及其与CKD患者病情进展的相关性.为后续大规模的临床验证研究奠定基础,为临床制定针对CKD患者的心理健康管理策略提供依据.并以此课题引起医务工作人员对CKD患者心理健康方面的重视,对患者进行早期心理干预,以达到延缓CKD进展,改善CKD患者的生活质量的目的.

目的:采用单侧输尿管结扎(UUO)方法建立肾间质纤维化模型大鼠,观察刺梨黄酮对UUO模型大鼠肾组织中氧化应激指标及TGF-β1、TGF-βR Ⅰ的影响.方法:将60只SD雄性大鼠适应性喂养1周后,随机分为假手术组(生理盐水)、模型组(生理盐水)、刺梨大剂量组(刺梨冻干粉)、刺梨中剂量组(刺梨冻干粉)、氯沙坦钾组(氯沙坦钾)各12只;除假手术组外,各组均行单侧输尿管结扎术(UUo),假手术组只行输尿管分离,但不结扎.各组于分组当天,均以相对应的药物灌胃,疗程14 d.应用比色法、免疫组织化法,Western blotting等检测技术,观察大鼠肾组织丙二醛(MDA)和超氧化物歧化酶(SOD)含量以及肾组织TGF-β1、TGF-βR Ⅰ的表达.结果:与假手术组比较,模型组病理损伤程度显著增加,MDA含量增加、SOD含量降低(P＜0.01),TGF-β1、TGF-βR Ⅰ的表达水平明显增加(P＜0.05).与模型组比较各治疗组病理损伤减轻,MDA含量降低、SOD含量升高,TGF-β1、TGF-βR Ⅰ表达减少(P＜0.05),跟剂量无关,中剂量组治疗疗效优于大剂量组(P＜0.05).中剂量组与氯沙坦钾组比较差异无显著性(P＞0.05).结论:刺梨黄酮与氯沙坦均能抑制单侧输尿管结扎肾间质纤维化大鼠的肾组织脂质过氧化物的产生,同时能增加抗氧化酶的含量,保护受损肾小管上皮细胞,有效改善肾脏纤维化病变,其机理可能与抗氧化应激、下调TGF-β1、TGF-βR Ⅰ的表达有关.