Expression and modulation of connective tissue growth factor in renal interstitial fibrosis

CTGF, a member of the CCN family of immediate early genes, is a recently discovered profibrotic growth factor, which is involved in many pathophysiologic procedures. CTGF acts as a downstream effector of TGF-β acting on interstitial cells to enhance the progression of fibrotic renal diseases. It has been shown that CTGF gene expression can be induced or blocked by some kinds of cytokine and drugs. It is an interesting candidate target for future intervention strategies of renal interstitial fibrosis.     

绵羊实验性乳酸酸中毒研究——Ⅲ.肾功能和尿液的改变

将12只2～3岁健康绵羊分为Ⅰ组(3只)、Ⅱ组(6只)和Ⅲ组(3只),分别按2.5,5.0,10.0 g/kg体重的剂量,向瘤胃内注入50%D—L消旋体乳酸溶液,各处理组均出现酸中毒症状.乳酸酸中毒时,肾脏的损伤程度与瘤胃内注入乳酸的剂量水平有关.各处理组瘤胃内注入乳酸后,尿素氮显著升高.第Ⅰ组尿液pH下降迅速,恢复亦快;第Ⅱ组尿液pH下降和回升均较缓慢,而且出现大量蛋白质和血液;第Ⅲ组尿液除见第Ⅰ、Ⅱ组的变化外,还出现肌红蛋白、酮体和尿胆素原.     

绿茶抗大鼠肾间质纤维化作用的实验研究

采用"单肾切除加腺嘌呤灌胃法"建立大鼠慢性肾衰竭模型。治疗组予绿茶液灌胃治疗,对照组予尿毒清溶液灌胃治疗,连续治疗28天。取大鼠肾脏石蜡切片分别进行HE染色、PASM染色、Masson染色、Sirius Red染色、Mallory染色,光镜下观察大鼠肾组织5种染色的病理形态学改变,PASM染色、Masson染色、Sirius Red染色随机选择进行肾脏组织病理学图像分析。绿茶组在肾间质纤维化面积、肾小球系膜积分光密度值、肾间质中I、Ⅲ型胶原分布面积等方面的作用与模型组对比,P<0.05。说明绿茶能够减轻腺嘌呤对大鼠肾间质的病理损害,绿茶有抗肾间质纤维化的作用,并且能抑制I、Ⅲ型胶原纤维的增生,这可能是绿茶防治肾间质纤维化、延缓慢性肾衰竭发展进程的机制之一。     

Experimental research on cardiac fibrosis induced by recombinant mouse interleukin-11 in mice

AIM To observe the effect of recombinant mouse interleukin-11 （rmIL-11）injected subcutaneously into mice on heart structure and function and to determine its pro-fibrotic effect. METHODS C57BL/6 mice were randomly divided into experimental group and control group.The mice in experimental group were injected subcutaneously with recombinant mouse IL-11 at the dose of 100 μg·kg^-1·d^-1 for 3 consecutive weeks, while the control group were given equal volume of normal saline in the same way. After the experiment was finished, the parameters of heart function were measured by echocardiography.The heart weight was weighed and the cardiac weight index (CWI) was calculated. HE staining and Masson's trichrome staining were performed to observe the pathological changes and the extent of myocardial fibrosis in mouse myocardia respectively, and the cardiac collagen volume fraction (CVF) was calculated. The expression levels of extracellular matrix proteins in the myocardial tissues of mice, including type Ⅰ collagen, type Ⅲ collagen and fibronectin, were determined by Western blot. RESULTS Left ventricular ejection fraction and left ventricular fraction shortening in experimental group were obviously lower than those in control group (P<0.01), however left ventricular end-diastolic diamension and left ventricular end systolic dimension were significantly higher than those in control group (P<0.05).Compared with control group, the CWI was increased (P<0.01), the myocardial arrangement was disorder, the necrosis of cardiac myocytes was increased, and excessive deposition of collagen was observed in the myocardial tissues in experimental group. Correspondingly, the CVF and protein levels of type Ⅰ collagen, type Ⅲ collagen and fibronectin in the left ventricle in experimental group were increased significantly (P<0.05). CONCLUSION Injection of rmIL-11 into the mice subcutaneously induces fibrogenesis in the heart, which implies that IL-11 is likely a novel pro-fibrotic factor.     

套式反转录—聚合酶链反应检测恙螨及鼠肺内肾综合征出血热病毒RNA

选择覆盖肾综合征出血热病毒（ＨＦＲＳＶ）膜蛋白（ＭＰ）基因的保守区核苷酸序列合成２对引物,采用异硫氰酸胍一步抽提ＲＮＡ,建立了ＲＴ－ＰＣＲ检测鼠体恙螨及游离恙螨体内ＨＦＲＳＶ－ＲＮＡ的方法,扩增产物经凝胶电泳及斑点印迹杂交证实具有特异性。结果显示,ＨＦＲＳＶ抗原阳性鼠体恙螨５０只组、１０只组、游离螨５０只组,ＨＦＲＳＶ抗原阳性鼠肺１０００ｍｇ、５００ｍｇ组经ＲＴ－ＰＣＲ检测为阳性;ＨＦＲＳＶ抗原阳性鼠体恙螨５只组,ＨＦＲＳＶ抗原阴性鼠体恙螨５０只和１０只组,游离螨１０只和５只组,鼠肺ＨＦＲＳＶ抗原阳性１００ｍｇ组均未见有明显扩增带。进一步用套式反转录－聚合酶链反应（ＮｅｓｔｅｄＲＴ－ＰＣＲ）检测,在ＲＴ－ＰＣＲ未测出ＨＦＲＳＶ－ＲＮＡ的各组中均检测有ＨＦＲＳＶ－ＲＮＡ。结果表明ＮｅｓｔｅｄＲＴ－ＰＣＲ具有高特异、高敏感的特点,可用于检测恙螨体内微量ＨＦＲＳＶ－ＲＮＡ,为确认恙螨作为ＨＦＲＳＶ的传播媒介提供了分子生物学证据。     

鸡尿酸盐沉积临床病理学实验研究

将２５６只３５日龄迪卡鸡随机分为对照、高蛋白Ⅰ、高蛋白Ⅱ、高钙和肾衰组,通过人工复制尿酸盐沉积病例,对禽痛风进行临床病理学研究。结果：（１）正常鸡血浆中约有０．１０７ｍｍｏｌ／Ｌ的尿酸与大分子（蛋白质）结合,当血浆尿酸浓度升高时,结合尿酸的浓度不变,游离尿酸水平升高;（２）高蛋白饲料使饮水增多,血浆尿酸、ＮＰＮ升高（Ｐ＜０．０１或Ｐ＜０．０５）,而肾脏菊糖清除率与对照组（３．２７２μｇ／ｋｇ．ｍｉｎ－１）差异不显著（Ｐ＞０．０５）,剖检未见痛风病变;（３）日粮高钙使采食量下降,增重降低,血浆钙、尿酸、ＮＰＮ升高（Ｐ＜０．０１或Ｐ＜０．０５）,肾菊糖清除率（２．７０９μｇ／ｋｇ．ｍｉｎ－１）与对照组差异不显著（Ｐ＞０．０５）,但死亡鸡中３／１１见肾和输尿管内有较多尿酸盐沉积;（４）肾脏损害使血浆尿酸、ＮＰＮ升高（Ｐ＜０．０１或Ｐ＜０．０５）,Ｎａ＋、总蛋白降低（Ｐ＜０．０５）,肾菊糖清除率显著低于对照组（Ｐ＜０．０５）,死亡鸡中１９／２７有明显肾脏肿大、肾和输尿管内沉积大量尿酸盐。     

Influence of paricalcitol on renal tubulointerstitial fibrosis in diabetic nephropathy

AIM: To investigate the effect of paricalcitol (P) on renal tubulointerstitial fibrosis and the underlying mechanisms in diabetic nephropathy (DN).METHODS: DN rat model was induced by a single intraperitoneal injection of streptozotocin after fasting. The animals were randomly divided into 2 groups:the DN rats in paricalcitol-intervened group (group P) were injected intraperitoneally with paricalcitol dissolved in propylene glycol after the day when the model was induced successfully at a dose of 0.4 μg/kg (3 times a week); the DN rats in DN group (group D) were given isopyknic propylene glycol. Normal control group (group C) was also set up. The samples of blood, urine and renal tissue were collected after intervention of paricalcitol for 12 weeks. The biochemical indexes were measured. The renal tissues were used for pathologic observation and determining the expression of transforming growth factor-β1 (TGF-β1), Wnt-4, β-catenin and Klotho by immunohistochemistry and Western blotting. In addition, the correlation among the above indexes was analyzed.RESULTS: (1) Scr, BUN and 24 h urine protein increased significantly in group D compared with group C, while decreased in group P compared with group D (P<0.05). (2) The area of renal tubulointerstitial fibrosis increased in group D compared with group C, while decreased in group P compared with group D (P<0.05). (3) The expression of Klotho decreased, while the expression of TGF-β1, Wnt-4 and β-catenin increased in group D compared with group C (P<0.05). Compared with group D, the expression of Klotho increased, while the expression of TGF-β1, Wnt-4 and β-catenin decreased in group P (P<0.05). (4) The expression of Klotho was negatively correlated with the fibrosis area, TGF-β1, Wnt-4 and β-catenin (P<0.05).CONCLUSION: Paricalcitol inhibits renal tubulointerstitial fibrosis in DN by promoting the expression of renal Klotho, and inhibiting Wnt/β-catenin signaling pathway activation and TGF-β1 synthesis.     

In-hospital development of an aorto-cardiac fistula in a Warmblood gelding with chronic renal disease

A 20-year-old Warmblood gelding presented for evaluation and treatment of ventral oedema and azotaemia of unknown aetiology. On presentation, a diastolic heart murmur was appreciated and echocardiography revealed moderate aortic insufficiency due to chronic degenerative valve disease. The horse was hospitalised and failed to respond to oral and i.v. fluids and diuretics. Following discontinuation of all fluid and diuretic therapy, the horse became acutely agitated and developed monomorphic ventricular tachycardia. The ventricular tachycardia spontaneously converted to normal sinus rhythm, however the heart murmur changed in timing to a right basilar continuous murmur and bounding jugular pulses were noted. Repeat echocardiogram revealed an aorto-cardiac fistula with dissection into the basilar interventricular septum and left-sided chamber volume overload that was not previously present. Attempts at stabilisation were unsuccessful and euthanasia was elected. Post-mortem examination confirmed chronic renal disease of unknown aetiology in addition to an aorto-cardiac fistula originating from the right sinus of Valsalva with subsequent dissection into the basilar interventricular septum.