自发性高血压大鼠心肌肥厚和心肌MAPK、AngⅡ的关系

放免法测定自发性高血压大鼠（ＳＨＲ）血浆及心肌血管紧张素Ⅱ（ＡｎｇⅡ）含量,凝胶内磷酸化法测定心肌丝裂素活化蛋白激酶活性（ＭＡＰＫ）,以心脏重／体重表示心肌肥厚程度。结果表明：与４个月的ＷＫＹ大鼠比较,４个月的ＳＨＲ血浆和心肌组织ＡｎｇⅡ及心肌ＭＡＰＫ活性分别增加了２１８．６％、１０１．２％和１０７．０％,心肌肥大程度严重,其中ＭＡＰＫ活性与心肌肥大程度呈明显正相关。提示４个月ＳＨＲ心肌肥厚可能是     

AngⅡ和PKC对心肌细胞AngⅡ 1型受体的转录调节

利用体外培养的心肌细胞,观察血管紧张素Ⅱ（ＡｎｇⅡ）和蛋白激酶Ｃ（ＰＫＣ）在诱导ＡｎｇⅡ１型受体（ＡＴ１）基因表达及蛋白质代谢中的作用．研究结果表明：ＡｎｇⅡ可诱导ＡＴ１ｍＲＮＡ水平一过性下调,呈时间及剂量依赖性,１０ｎｍｏｌ／ＬＡｎｇⅡ刺激细胞６ｈ,引起ＡＴ１ｍＲＮＡ水平降低幅度最大,降至对照的５１．６％±９．５％,然后逐渐回升,２４ｈ恢复至对照水平．３０μｍｏｌ／ＬＨ－７（ＰＫＣ抑制剂）能阻断ＡｎｇⅡ诱导的ＡＴ１ｍＲＮＡ水平的下调．０．３μｍｏｌ／Ｌ的ＰＭＡ（ＰＫＣ激活剂）单独应用可诱导ＡＴ１ｍＲＮＡ水平下调达对照的４３％±８％,加入ＡＴ１拮抗剂ＤＭＰ８１１及Ｄｕｐ７５３均可阻断ＡｎｇⅡ诱导的ＡＴ１ｍＲＮＡ水平的下调．１０ｎｍｏｌ／Ｌ的ＡｎｇⅡ刺激心肌细胞９６ｈ可使蛋白含量降低至对照的７３．４％±５．６％,而加药持续刺激１４４ｈ可使蛋白含量较对照增加３３．８％±６．３％,Ｈ－７不能阻断ＡｎｇⅡ诱导的蛋白含量降低,但可有效地抑制蛋白含量的增加．以上结果提示：ＡｎｇⅡ对心肌细胞ＡＴ１基因的转录和细胞的蛋白代谢有调节作用,而ＰＫＣ则参与了ＡｎｇⅡ的这种调节作用     

氯沙坦对肾血管性高血压大鼠血清中血管紧张素Ⅱ-1受体自身抗体产生的影响

目的和方法：采用两肾一夹型肾血管性高血压（RVH）模型,以合成的大鼠血管紧张素Ⅱ－1受体（AT1R）细胞外第二环165－191位氨基酸序列作为特异性抗原,用ELISA法检测大鼠血清中血管紧张素Ⅱ－1受体自身抗体,动态观察（13周）氯沙坦（术后第2周开始,5mg/kg dig,连续12周）治疗对模型大鼠AT1R自身抗体产生的影响。结果：RVH组大鼠血清中AT1R自身抗体从术后1周起阳性率、滴度逐渐升高;给予氯沙坦治疗不仅可抑制模型大鼠心脏功能和结构的改变,而且使血清AT1R自身抗体的阳性率和滴度明显低于肾血管性高血压组。结论：氯沙坦有抑制AT1R自身抗体产生而达到降压的作用。     

大鼠脑室内注射ANGⅡ和ANGⅡ抗体对尿钠排出和肾皮质...

In anesthetized rats, it was observed that intracerebroventricular (I.C.V.) microinjection of angiotensin II (ANG II) in a dose of 16 pg evoked a significant increase in renal sodium excretion which began within 15 min and lasted for 90 min. The activity of Na+.K(+)-ATPase in renal cortex after I.C.V. microinjection of ANG II (1.51 +/- 0.26 mumol Pi/mg Pro.h) was inhibited as compared with that of the control injecting of artificial cerebrospinal fluid (2.66 +/- 0.28 mumol Pi/mg Pro.h, P less than 0.01). There was no change in mean arterial pressure. Within 15 min after I.C.V. administration of ANG II antibody, however, and antinatriuretic period of 135 min and a higher activity of Na+.K(+)-ATPase in renal cortex (3.61 +/- 0.34 mumol Pi/mg Pro.h, P less than 0.05 compared with control) were observed. There was no natriuresis in the animals microinjected with ANG II either into femoral vein or into spinal subarachnoid space. The result of the present investigation suggests that brain endogenous ANG II may possess some natriuretic activity possibly through inhibiting renal Na+.K(+)-ATPase activity.     

慢性肾衰病人血浆MMS对大鼠心脏活动能力的影响

血浆中分子物质 (ＭＭＳ)是分子量在 30 0～ 5 0 0 0Ｄａｌｔｏｎ之间的一类多肽。有实验证明 :肾衰患者血浆ＭＭＳ在体外可抑制大鼠膈肌切片、肾皮质、大脑皮质和人类红细胞对葡萄糖的摄取 ,可抑制腺苷酸环化酶、Ｎａ Ｋ ＡＴＰ酶的活性。ＭＭＳ影响机体多种酶的活性及膜的物质转运 ,势必会导致心肌的电生理特性及心肌舒缩能力的变化 ,甚至出现尿毒症性心肌病。本实验目的在于观察ＭＭＳ对心肌舒缩能力的影响 ,为肾衰患者的心功能改变及治疗提供理论基础。1　材料与方法(1)ＭＭＳ的分离与测定　取正常人和慢性肾衰 (尿毒症期 )患者空腹血 …     

葛根素对甘油致急性肾功能衰竭兔血液流变学和肾血流量的影响

目的 肌注甘油复制急性肾功能衰竭(ARF)兔模型,观察葛根素(Pue)对ARF兔血液流变学和肾血流量的影响.方法 健康雄性日本大耳白兔30只,随机分为正常组、ARF模型组、Pue 1组(20 mg/kg)、Pue 2组(40mg/kg)、Pue 3组(80 mg/kg).各组于不同时间点测量其肾血流量、血液流变学指标和肾功能指标(Cr、BUN),并观察肾组织形态学改变.结果 与模型组比较,Pue 2组和Pue 3组治疗后各时间点Cr、BUN降低(P＜0.05),血液流变学指标降低明显(P＜0.05),肾血流量增加差异具有统计学意义(P＜0.05).Pue 2组和Pue 3组肾小管上皮细胞肿胀减轻,管型少见.结论 葛根素可明显改善急性肾功能衰竭兔血液流变性,增加肾血流量,进而达到改善、减轻肾小管损害的作用.     

血管紧张素Ⅱ对大鼠下丘脑内血管升压素基因转录的影响

实验在雄性ＳＤ大鼠中进行,用核酸斑点杂交技术观察下丘脑组织中血管升压素（ＡＶＰ）基因转录水平变化,用异羟基洋地黄毒甙（ＧＩＧ）标记的２６个碱基长寡聚核苷酸作为检测探针。实验中观察到,用渗透压微泵向大鼠侧脑人连续注射微量血管紧张素Ⅰ（０．２ｎｍｏｌ／ｈ）２ｄ后,可引起动物饮水量显著增加,下丘脑组织中ＡＶＰ基因转录水平高,但无统计学显著意义。将实验动物日饮水量限制在与对照动物相同的每日饮水量之后,侧脑     

茶多酚和艾司洛尔对高AngⅡ状态下血管内皮细胞内皮素分泌的影响

目的：探讨茶多酚和艾司洛尔能否对模拟失重所致的高AngⅡ状态的损害提供保护。方法：将培养的血管内皮细胞分为空白对照组、单纯血管紧张素Ⅱ组、血管紧张素Ⅱ＋茶多酚组、血管紧张素Ⅱ＋艾司洛尔组共4组,用放免法测定在不同时间内皮细胞分泌内皮素含量的变化。结果：AngⅡ可明显促进血管内皮细胞分泌内皮素,茶多酚和艾司洛尔能明显抑制高AngⅡ致血管内皮细胞分泌内皮素的作用（P〈0．01）,茶多酚的作用较艾司洛尔的更强（P〈0．01）。结论：茶多酚和艾司洛尔可减轻高AngⅡ状态的损害作用。     

自发性高血压大鼠中枢血管紧张素Ⅱ的变化对中枢肾上腺素...

The content of norepinephrine (NE) and epinephrine (E) in the brain of spontaneously hypertensive rats has proved abnormal, but the cause remained unknown. It was shown in the recent work that NE content in pons, posterior hypothalamus, nucleus caudatus and E concentration in medulla oblongata, anterior and posterior hypothalamus of 12-week old stroke-prone spontaneously hypertensive rats (SHRSP) were much higher than those of age-matched Wister-Kyoto rats (WKY). SHRSP also showed higher levels of systolic blood pressure (SBP) and brain angiotensin II (A II) than WKY. Intracerebroventricular (icv) perfusion of angiotensin-converting enzyme inhibitor captopril (20 micrograms for each time and three times for each day for four weeks) inhibited the synthesis of brain A II and reduced SBP and NE, E contents in all examined brain areas in SHRSP and WKY. However, the effects of chronically perfused captopril on SBP and brain NE, E levels in SHRSP were much more significant than in WKY. The results indicate that the modulatory effects of central renin-angiotensin system (RAS) on central adrenergic and noradrenergic system might be overactivated in SHRSP, which might partially responsible for the abnormally high levels of NE, E in some of the brain areas of SHRSP.     

肾性和自发性高血压大鼠心肌肥大前后心肌Gαq/11含量的变化

目的 :探讨Gαq/11在不同原因所致心肌肥大中的变化。方法 :两肾一夹肾性高血压大鼠 (RHR)和自发性高血压大鼠(SHR)模型 ,测定动脉血压和心肌肥大指数 ,放免法测定心肌血管紧张素II(AngII)含量 ,免疫印迹法测定心肌Gαq/11含量。 结果 :RHR术后 1周动脉血压、心肌肥大指数及Gαq/11含量与假手术组无差异 ,心肌AngII含量显著升高 (P <0 .0 1) ;术后 8周上述各指标均较假手术组升高。 12周龄SHR动脉血压、心肌肥大指数和AngⅡ含量均较同龄WKY升高 (P均 <0 .0 1) ,但心肌Gαq/11含量却无明显变化 ;4周龄时上述各指标与同龄对照相比均无明显差异。 结论 :Gαq/11在肾性和自发性高血压心肌肥大中有不同变化。     

Endogenous angiotensin II and the regulation of oxygen consumption and colonic temperature in rats

Previous studies have suggested that angiotensin II, a hormone known to regulate water and salt balance and blood pressure, may also regulate oxygen consumption and body temperature. In this study we investigated the role of endogenous angiotensin in the regulation of oxygen consumption and colonic temperature in rats under low (control) and high (water deprivation, administration of isoproterenol and hemorrhage) peripheral angiotensin conditions. Peripheral administration of losartan, an AT₁ receptor antagonist or enalapril, an angiotensin converting enzyme inhibitor, did not alter oxygen consumption or colonic temperature in control or water deprived rats. Peripheral administration of losartan did not alter the oxygen consumption and colonic temperature responses to the administration of isoproterenol or hemorrhage. Endogenous peripherally generated angiotensin II does not play an important role in regulating either oxygen consumption or colonic temperature in rats under either low or high angiotensin II levels. The reductions in oxygen consumption and colonic temperature that accompany hemorrhage in rats are not mediated by angiotensin II.     

Effect of Acacia gum on blood pressure in rats with adenine-induced chronic renal failure

Chronic renal failure (CRF) occurring naturally in patients or induced by subtotal nephrectomy in rats induces several alterations in the cardiovascular system (CVS). However, the effect of chemically induced CRF in rats on the CVS is less well known. We induced CRF in rats by feeding adenine (0.75%, w/w, four weeks) and investigated the effect of the ensuing CRF on the systolic and diastolic blood pressure (BP) and heart rate (HR). Further, we investigated the effect of giving acacia gum (AG, 10%, w/v) in the drinking water concomitantly with adenine on the above parameters. AG has been previously shown to ameliorate the severity of CRF in humans and rats. We confirmed here that adenine-induced CRF significantly increased the plasma concentrations of urea and creatinine, and reduced creatinine clearance. Additionally, it significantly increased both systolic and diastolic BP, with no significant effect on HR. Both of these actions were significantly mitigated by AG treatment. The antihypertensive angiotenisn-converting enzyme inhibitor lisinopril (10 mg/kg) was given by gavage to rats concomitantly with adenine, significantly reduced the rise in blood pressure induced by adenine. In conclusion, adenine-induced CRF in rats significantly increased BP, and this was significantly mitigated by administration of AG. Possible mechanisms of these changes and the protective effect of AG will be investigated.     

Effects of angiotensin II on the spontaneous activity of rostral ventrolateral medullary cardiovascular neurons and blood pressure in spontaneously hypertensive rats

The interactive role of rostral ventrolateral medulla (RVL) cardiovascular neurons and brain angiotensin II (Ang II) in regulating the arterial blood pressure was examined by recording simultaneously the spontaneous activity of these spinal projecting neurons and the arterial blood pressure in the pentobarbital-anesthetized spontaneously hypertensive rat (SHR) and its normotensive control, the Wistar Kyoto rat (WKY). It was found that Ang II elicited dose-dependent excitatory responses in a subpopulation of RVL cardiovascular neurons, followed by a subsequent increase in blood pressure. These effects of Ang II were significantly greater in SHR than in WKY. The effects were attenuated or abolished by co-administration of Ang II antagonist, [Sar¹, Ile⁸]-Ang II. Pre-administration of [Sar¹, Ile⁸]-Ang II to RVL using bilateral microinjection attenuated the blood pressure effects of intracerebroventricularly administered Ang II by as much as 70%. These results indicated that spinal projecting RVL cardiovascular neurons are important in mediating the pressor action of Ang II. The enhanced sensitivity and responsiveness of RVL cardiovascular neurons to Ang II may be pertinent to the genesis of hypertension in adult SHR.     

Effects of a new amino acid supplement on blood AA pools in patients with chronic renal failure

Summary We designed a new formula for AA supplement in order to correct blood pools of AA in chronic renal failure (CRF). This supplement was given to 5 patients with CRF and its effectiveness was tested during long term (12–24 weeks) administration. The patients had previously been on a diet providing 0.6 g of protein and 34–36 kcal/kg/day. The diet was then modified to one providing the same caloric content but only 0.3 g/kg high biological value protein per day with the addition of the AA supplement (0.3 g/kg). The new diet corrected most of the abnormalities in blood AA pools. After 1 month of treatment Val, Leu, Thr, Ser and Tyr levels rose and became normal throughout the study. Ratios Tyr/Phe, Ser/Gly and Val/Gly also improved. During the treatment no side effect or toxicity was observed, and serum albumin, transferrin and nutritional anthropometric parameters persisted to be normal. It is concluded that this specially designed AA supplement added to a hypoproteic diet is an acceptable regimen which can quite completely correct the imbalance in blood AA pools in CRF.     

Complementary effects of adenosine and angiotensin II in hypoxemia-induced renal dysfunction in the rabbit

The acute renal effects of hypoxemia and the ability of the co-administration of an angiotensin converting enzyme inhibitor (perindoprilat) and an adenosine receptor antagonist (theophylline) to prevent these effects were assessed in anesthetized and mechanically-ventilated rabbits. Renal blood flow (RBF) and glomerular filtration rate (GFR) were determined by the clearances of para-aminohippuric acid and inulin, respectively. Each animal acted as its own control. In 8 untreated rabbits, hypoxemia induced a significant drop in mean blood pressure (-12 +/- 2%), GFR (-16 +/- 3%) and RBF (-12 +/- 3%) with a concomitant increase in renal vascular resistance (RVR) (+ 18 +/- 5%), without changes in filtration fraction (FF) (-4 +/- 2%). These results suggest the occurrence of both pre- and postglomerular vasoconstriction during the hypoxemic stress. In 7 rabbits pretreated with intravenous perindoprilat (20 microg/kg), the hypoxemia-induced changes in RBF and RVR were prevented. FF decreased significantly (-18 +/- 2%), while the drop in GFR was partially blunted. These results could be explained by the inhibition of the angiotensin-mediated efferent vasoconstriction by perindoprilat. In 7 additional rabbits, co-administration of perindoprilat and theophylline (1 mg/kg) completely prevented the hypoxemia-induced changes in RBF (+ 11 +/- 3%) and GFR (+ 2 +/- 3%), while RVR decreased significantly (-14 +/- 3%). Since adenosine and angiotensin II were both shown to participate, at least in part, in the renal changes induced by hypoxemia, the beneficial effects of perindoprilat and theophylline in this model could be mediated by complementary actions of angiotensin II and adenosine on the renal vasculature.     

肾康注射液联合血液透析治疗慢性肾功能衰竭的临床效果及对肾功能、营养指标的影响

目的 探讨肾康注射液联合血液透析治疗对慢性肾功能衰竭患者的肾功能、营养指标及临床疗效的影响.方法 选取2018年3月～2019年2月我院肾内科收治的116例慢性肾功能衰竭患者作为研究对象,随机分为对照组和观察组各58例.对照组给予单纯血液透析治疗,观察组给予肾康注射液联合血液透析治疗,治疗16周后观察两组患者的肾功能及...     

Angiotensin II type 1 receptor blockade attenuates renal fibrogenesis in an immune-mediated nephritic kidney through counter-activation of angiotensin II type 2 receptor

The relative roles of angiotensin II (Ang II) type 1 receptor (AT(1)R) and Ang II type 2 receptor (AT(2)R) in immune-mediated nephritis are unknown, and the effect of the blockade of AT(1)R and its indirect counter-activation of AT(2)R relative to the anti-fibrotic action in this disease is unclear. To address this question, we studied the role of AT(1)R and AT(2)R in anti-glomerular basement membrane nephritis in SJL mice. Groups of mice were treated with either an AT(1)R antagonist (CGP-48933; CGP group), an AT(2)R antagonist (PD-123319; PD group), both (CGP/PD group), or a vehicle (PCt group) from Day 29 to 56. At Day 56 post-treatment, fibrosis-related parameters such as interstitial matrix deposition, and the expression of genes of TGF-beta1, plasminogen activator inhibitor-1, and type I collagen were significantly reduced in the kidney in the CGP group. There were no significant effects on these parameters in the PD group. However, this anti-fibrotic action by CGP-48933 was totally abolished by co-treatment with PD-123319 in the CGP/PD group. The gene expression of renin was significantly increased in the kidneys in the CGP and CGP/PD groups, suggesting that CGP-48933 had increased Ang II generation in those groups. In conclusion, counter-activation of AT(2)R by increased Ang II under AT(1)R blockade likely conferred an anti-fibrotic protection in this model.     

内毒素在大剂量顺铂所致大鼠急性肾损伤过程中的变化及意义

目的利用大剂量顺铂（cisplatin,DDP）所致大鼠急性肾功能衰竭的动物模型,观察外周血内毒素（endotoxin）在大鼠急性肾损伤中的变化及其意义。方法SD大鼠36只,雌雄各半,依体重随机分为DDP用药6h、48h、对照组和生理盐水（NS）用药6h、48h、对照组,每组6只。10mg／kgDDP单次腹腔内注射,等量Ns对照。观察并记录用药后对照组大鼠的毒副反应;用药6、48h各组大鼠无菌条件下心脏穿刺取血、肝素抗凝,检测外周血内毒素含量,同时内眦静脉取血,测定血清尿素氮、肌酐浓度,并进行统计学分析。结果DDP用药后6h,大鼠体重开始明显降低,用药48h后,大鼠腹泻逐渐加重,用药3d后大鼠死亡。DDP用药后6h大鼠血尿素氮、肌酐的含量与对照组比较差异无显著性（P〉0．05）;DDP用药后48h血尿素氮升至（18．71±9．9）mmol／L,明显高于对照组（7．48±0．6）mmol／L（P〈0．05）,同时血肌酐含量亦升至（49．6±14．1）μmol／L,与对照组（27．17±1．7）μmol／L比较差异具有显著性（P〈0．05）。DDP用药后6h所有大鼠外周血内毒素含量都低于0．0218Eu／rrd最低检出限,明显低于NS对照组大鼠（0．3141±0．1477）Eu／ml（P〈0．01）;DDP用药后48h大鼠外周血内毒素的含量增高均超过0．70Eu／ml最高检出限,明显高于NS对照组大鼠（0．1661±0．1198）Eu／ml（P〈0．01）。结论外周血内毒素含量的变化与大剂量顺铂所致大鼠急性肾损伤早期的发病机制无关,但与大鼠肾功能衰竭有关的发生相关。     

Effects of oxygen free radical scavengers on uranium-induced acute renal failure in rats

Study was made to determine whether oxygen free radicals mediate uranium-induced acute renal failure (ARF). Superoxide dismutase (SOD), a superoxide anion scavenger, did not prevent uranium acetate (UA) (5 mg/kg, i.v.)-induced renal injury 48 h after injection. In contrast, dimethylthiourea (DMTU), a hydroxyl radical scavenger, significantly attenuated UA-induced rise in serum creatinine concentration (1.11 ± 0.05 (DMTU) vs. 1.40 ± 0.06 mg/dl (control), p < .05), and tubular necrosis. Dimethyl sulfoxide (DMSO), a hydroxyl radical scavenger, decreased UA-induced tubular damage. UA injection caused no increase in renal cortical malondialdehyde (MDA) content. DMTU and DMSO did not modify intrarenal MDA content. UA administration brought about significant increase in plasma renin activity but not in renal cortical renin content. Treatment with DMTU and DMSO had no effect on plasma renin activity or intrarenal renin content. It follows from these findings that DMTU and DMSO may attenuate UA-induced renal injury. Such a protective effect would not be mediated through modulation of lipid peroxidation or renin activity.     

Selenium and glutathione peroxidases in blood of patients with different stages of chronic renal failure

In patients with chronic renal failure (CRF) Se concentration in blood components is usually lower as compared with healthy controls. One of the five known forms of Se-dependent glutathione peroxidases (GSH-Px), the plasma GSH-Px, is synthesized primarily in the kidney. In CRF patients, plasma GSH-Px activity is reduced and the reduction increases with the progress of the disease.

The Se concentration in blood components was measured spectrofluorometrically with 2,3-diaminonaphthalene as complexing reagent. Activities of GSH-Px in red cells and in plasma were assayed by the coupled method with t-butyl hydroperoxide as substrate. The study group consisted of 150 patients in different stages of CRF. The results were compared with the values for 30 healthy subjects.

Se concentrations in whole blood and plasma of the entire group of patients were significantly lower (p < 0.01) as compared with the healthy subjects. In the incipient stage, however, the Se levels in all blood components were non-significantly lower. In whole blood and plasma the Se levels gradually decreased, reaching in the end stage values that were lower by 29 to 32% (p < 0.0001) as compared with the control group. Total protein and albumin levels in plasma of patients were significantly lower (p < 0.0001) as compared with healthy subjects and they decreased linearly with the progress of the disease. Positive and highly significant correlations were noted between total plasma protein and plasma Se concentrations (p < 0.0001) as well as between plasma albumin and plasma Se concentrations (p < 0.0001).

Red cell GSH-Px activity in the entire group of patients was lower (p < 0.05) than in the control group and did not change significantly with the progress of the disease. In plasma, however, GSH-Px activity of the entire group was lower by 33% (p < 0.0001) as compared with healthy subjects and decreased gradually with increasing renal failure. Highly significant, inverse correlations were seen between creatinine levels and plasma GSH-Px activities (p < 0.0001) as well as between urea nitrogen levels and plasma GSH-Px activities (p < 0.0001) when all stages of the disease were included.

In conclusion, patients with CRF exhibit lower Se levels in blood components as compared with healthy subjects. In whole blood and plasma these levels decrease with the progress of the disease. Plasma GSH-Px activity in patients was extremely reduced and it dramatically decreased with the progress of the illness.