Shen Qi Wan attenuates renal interstitial fibrosis through upregulating AQP1 / 中国天然药物

Renal interstitial fibrosis (RIF) is the crucial pathway in chronic kidney disease (CKD) leading to the end-stage renal failure. However, the underlying mechanism of Shen Qi Wan (SQW) on RIF is not fully understood. In the current study, we investigated the role of Aquaporin 1 (AQP1) in SQW on tubular epithelial-to-mesenchymal transition (EMT). A RIF mouse model induced by adenine and a TGF-β1-stimulated HK-2 cell model were etablished to explore the involvement of AQP 1 in the protective effect of SQW on EMT in vitro and in vivo. Subsequently, the molecular mechanism of SQW on EMT was explored in HK-2 cells with AQP1 knockdown. The results indicated that SQW alleviated kidney injury and renal collagen deposition in the kidneys of mice induced by adenine, increased the protein expression of E-cadherin and AQP1 expression, and decreased the expression of vimentin and α-smooth muscle actin (α-SMA). Similarly, treatmement with SQW-containing serum significantly halted EMT process in TGF-β1 stimulated HK-2 cells. The expression of snail and slug was significantly upregulated in HK-2 cells after knockdown of AQP1. AQP1 knockdown also increased the mRNA expression of vimentin and α-SMA, and decreased the expression of E-cadherin. The protein expression of vimentin increased, while the expression of E-cadherin and CK-18 significantly decreased after AQP1 knockdown in HK-2 cells. These results revealed that AQP1 knockdown promoted EMT. Furthermore, AQP1 knockdown abolished the protective effect of SQW-containing serum on EMT in HK-2 cells. In sum, SQW attentuates EMT process in RIF through upregulation of the expression of AQP1.

The distribution and function of aquaporin 1 and 2 along the kidney in different species / Distribución y función de la acuaporina 1 y 2 a lo largo del riñón en diferentes especies

SUMMARY: Water metabolism in kidney is critical for organisms living in arid environments. In this study, the kidney structure and the expression of AQP1 and AQP2 in Phrynocephalus vlangalii and Camelus bactrianus were studied. It was found that the Phrynocephalus vlangalii has fewer renal corpuscle but developed kidney tubules, and AQP1 and AQP2 were mainly expressed in the kidney tubules. Camelus bactrianus has a large diameter of glomerulus, thick bulbar membrane, and long and dense urinary tract. AQP1 was highly expressed in the proximal convoluted tubule, proximal straight tubule, and Ansa nephroni (Henle´s loop), and AQP2 was also highly expressed in the collecting tubule and distal convoluted tubule. In the long-term evolutionary adaptation, the morphological structure of animal kidney is consistent with its environment. In addition to structural and functional adaptation, aquaporin also participates in the adaptation to water scarcity environment, and may also play a key role.

RESUMEN: El metabolismo del agua en los riñones es fundamental para los organismos que viven en ambientes áridos. En este estudio, se estudió la estructura renal y la expresión de AQP1 y AQP2 en Phrynocephalus vlangalii y Camelus bactrianus. Se encontró que Phrynocephalus vlangalii tiene menos corpúsculos renales. pero desarrolló túbulos renales, y AQP1 y AQP2 se expresaron principalmente en los túbulos renales. Camelus bactrianus tiene un glomérulo de gran diámetro, una membrana bulbar gruesa y un tracto urinario largo y denso. AQP1 se expresó en gran medida en el túbulo contorneado proximal, el túbulo recto proximal y el Ansa nephroni o asa nefrónica (asa de Henle), y AQP2 también se expresó en gran medida en el túbulo colector y el túbulo contorneado distal. A largo plazo, en la adaptación evolutiva la estructura morfológica del riñón animal es coherente con su entorno. Además de la adaptación estructural y funcional, la acuaporina también es parte de la adaptación al entorno de escasez de agua y puede desempeñar un papel clave.

Different expressions of AQP1 and AQP4 in hyponatremic rat brain / Diferentes expresiones de AQP1 y AQP4 en cerebro de rata hiponatrémico

SUMMARY: The expression of aquaporin-1 (AQP1) in choroid plexus and aquaporin-4 (AQP4) in astrocyte of the hippocampal formation (HF) was studied in the rat to determine the role of AQP1 and AQP4 in the pathophysiology of systemic hyponatremia (SH). SH was induced by coadministration of dextrose solution intraperitoneally and through subcutaneous implantation of an osmotic minipump containing 8-deamino-arginin vasopressin (50ng/µl/h) for 24 and 48 h. Twenty- four and 48 h after the drug administration, there were significant reductions in Na+ concentration (111 ± 5 and 104 ± 2 mmol) and serum osmolarity (240 ± 13 and 221 ± 14 mOsm/L) as compared with control values (140 ± 4.7 mmol and 296 ± 5.2 mOsm/L), (p<0.01). The expression of AQP1 in the choroid plexus was increased three to five times from 24 h to 48 h after SH (329.86 ± 10.2 % and 531.5 ± 4.4 %, n=4, p<0.01). In contrast, AQP4 expression was significantly decreased up to 48 h after SH (36 ± 9 %, n=4, p<0.01). Quantitative immunoblotting revealed significant decreases of neuronal proteins in the HF after 24 to 48 h of SH. Therefore, we suggest that altered expression of AQP1 and AQP4 plays important role in the pathogenesis of systemic hyponatremia.

RESUMEN: En este análisis se estudió la expresión de acuaporina-1 (AQP1) en plexo coroideo y acuaporina-4 (AQP4) en astrocitos de la formación hipocampal (FH) en ratas para determinar el papel de AQP1 y AQP4 en la fisiopatología de la hiponatremia sistémica (HS). La HS fue inducida mediante la coadministración de solución de dextrosa por vía intraperitoneal y mediante la implantación subcutánea de una minibomba osmótica que contenía vasopresina 8-desaminoarginina (50 ng /µ l / h) durante 24 y 48 h. Veinticuatro y 48 h después de la administración del fármaco, hubo reducciones significativas en la concentración de Na + (111 ± 5 y 104 ± 2 mmol) y la osmolaridad sérica (240 ± 13 y 221 ± 14 mOsm /µL) en comparación con los valores de control (140 ± 4,7 mmol y 296 ± 5,2 mOsm / L), (p <0,01). La expresión de AQP1 en el plexo coroideo se incrementó de tres a cinco veces de 24 a 48 h después de HS (329,86 ± 10,2 % y 531,5 ± 4,4 %, n = 4, p <0,01). Por el contrario, la expresión de AQP4 se redujo significativamente hasta 48 h después de HS (36 ± 9 %, n = 4, p <0,01). La inmunotransferencia cuantitativa reveló disminuciones significativas de proteínas neuronales en el FH después de 24 a 48 h de SH. Por lo tanto, sugerimos que la expresión alterada de AQP1 y AQP4 juega un papel importante en la patogénesis de la hiponatremia sistémica.

Discovery of novel diarylamides as orally active diuretics targeting urea transporters

Urea transporters (UT) play a vital role in the mechanism of urine concentration and are recognized as novel targets for the development of salt-sparing diuretics. Thus, UT inhibitors are promising for development as novel diuretics. In the present study, a novel UT inhibitor with a diarylamide scaffold was discovered by high-throughput screening. Optimization of the inhibitor led to the identification of a promising preclinical candidate,

Las Aquaporinas Y El Sistema Nervioso Central / Aquaporins And System Nervous Central

RESUMEN El descubrimiento de las acuaporinas, que constituyen una familia de proteínas integrales de membrana, ha supuesto un cambio con respecto a la comprensión del transporte de agua en las membranas biológicas. La más importante es la aquaporina 4 (AQP4) en la que nos centraremos a continuación, aunque existen otras dos acuaporinas la 1y la 9. Estas acuaporinas tienen una gran importancia en la fisiología del control del volumen celular y los mecanismos de control osmótico de las células. También en el control del flujo de glicerol y otros solutos. Además, las alteraciones en su funcionamiento se han relacionado con distintas enfermedades del sistema nervioso central como la neuromielitis óptica, el edema cerebral, la hipertensión intracraneal idiopática o la hidrocefalia crónica del adulto entre otras. Se realiza una revisión sobre este tema.

ABSTRACT The discovery of aquaporins, which constitute a family of integral membrane proteins, has meant a change with respect to the understanding of water transport in biological membranes. The most important is aquaporin 4 (AQP4) which we will focus on below, although there are two other aquaporins, 1 and 9. These aquaporins are of great importance in the physiology of cell volume control and osmotic control mechanisms of the cells. Also in the control of the flow of glycerol and other solutes. In addition, alterations in its functioning have been related to various diseases of the central nervous system such as neuromyelitis optics, cerebral edema, idiopathic intracranial hypertension or chronic hydrocephalus of the adult among others. A review is made on this topic.

Immunohistochemical study of aquaporin 1 and 2 in the hepatobiliary system of Qinghai lizard (Pphrynocephalus vlangalii ) / Estudio inmunohistoquímico de aquaporin 1 y 2 en la sistema hepatobiliar del lagarto de Qinghai ( Phrynocephalus vlangalii )

A serous membrane covering the liver and the hepatic parenchyma, consists of hepatocytes, arteries, veins, hepatic sinusoids and biliary ductuli. There are erythrocytes, thrombocytes, melanin particles and Kupffer cell in the hepatic sinusoids and the blood vessels. The gall bladder wall consists of a mucous layer a muscle layer and a serous layer. The bottom of the epithelium abounds with round or oval secretory. In liver, immunohistochemistry results show that AQP1 have intense reaction in hepatic lobule, Kupffer cells (Macrophagocytus stellatus), hepatocytes, portal tract, blood islands, vein and artery, but almost no reaction of AQP2 was detected. In gallbladder, mucous epithelium, endothelial cells from vein and artery all have strong AQP1 expression, AQP2 showed minor diffused positive reaction in gallbladder, which suggesting that AQP1 may have the main role in the absorption and transportation of fluid in hepatobiliary system of Qinghai Lizard.

Una membrana serosa cubre el hígado y el parénquima hepático el cual está formado por hepatocitos, arterias, venas, sinusoides hepáticos y conductos biliares. Se encuentran eritrocitos, trombocitos, partículas de melanina y células de Kupffer en los sinusoides hepáticos y en los vasos sanguíneos. La pared de la vesícula biliar presenta tres capas: mucosa, muscular y serosa. En el hígado, la inmunohistoquímica mostró que AQP1 tiene una reacción intensa en el lóbulo hepático, células de Kupffer, hepatocitos, tracto portal e islotes sanguíneos. En venas y arterias, no se detectó reacción alguna de AQP2. En la vesícula biliar, el epitelio mucoso, las células endoteliales venosas y arteriales tuvieron una importante expresión de AQP1, sin embargo, AQP2 mostró una reacción positiva difusa menor, lo que sugiere que la AQP1 podría tener una función principal en la absorción y transporte de líquido en el sistema hepatobiliar del Lagarto Qinghai.

Advances on distribution and function of aquaporin 1 in the peripheral nervous system / 第二军医大学学报

Aquaporin 1 (AQP1) is an aquaporin distributed in the peripheral nervous system. It has been found in neurons and glial cells of peripheral nerve structures, including trigeminal ganglion, dorsal root ganglion and enteric nervous system. AQP1 may be involved in the regulation of water balance of ganglia and nerve fiber bundles in the peripheral nervous system under physiological and pathological conditions, and plays a key role in maintaining the intracellular and extracellular water balance of peripheral nervous system under pathological condition. Knowing the structure and function of AQP1 can contribute to the understanding of the pathophysiology of the nervous system, providing new ways and methods for clinical treatment. This review summarizes the recent researches on AQP1.

Effect of erythropoietin on the eXpression and function of renal aquaporin－1 after release of bilateral ureter obstruction in young rats / 中华实用儿科临床杂志

Objective To investigate the effect of erythropoietin(EDO)on the expression and function of aqua_porin_1( AQD _1)in the kidney of young male SD rats after release of bilateral ureter obstruction( BUO _ R). Methods Porty_eight young SD rats were randomly divided into bilateral ureteral complete obstruction(BUO)group (n﹦6),BUO_R group(n﹦12),BUO_R﹢EDO group( n﹦12)and Sham group( n﹦18). The BUO model was built through bilateral ureteral ligation. BUO group were killed after 24 h,and BUO_R group and BUO_R﹢EDO group were relieved after obstruction of 24 h. EDO(500 U∕kg)was given to BUO_R﹢EDO rats at 1 h after release of BUO,and then repeated 1 d,3 d and 5 d thereafter and the same volume of 9 g∕L saline was simultaneously given to BUO_R rats. The Sham group was prepared in parallel by laparotomy and free dissection of bilateral ureters but not ligated,both side kidneys and blood samples were collected on 3 d and 7 d(24 h,3 d,7 d for Sham group)after release of BUO. The u_rine samples were collected by using metabolic cage before death. The plasma osmotic pressure,creatinine(Cr)and u_rea nitrogen(BUN)in the plasma of young rats were detected. The expression of AQD_1 protein in all groups of kidney tissues was detected by adopting immunohistochemistry and Western blot. Results On day 3 after release of BUO,24 h water intake and urine volume of BUO_R﹢EDO group were higher than those of Sham group,but lower than those of BUO group(P〈0. 05),the urine osmotic pressure of BUO_R﹢EDO group was higher than that of BUO group,but lower than that of Sham group(P〈0. 05),while plasma osmotic pressure,Cr and BUN of BUO_R﹢EDO group were higher than those of Sham group,but lower than those of BUO group(P〈0. 05),and they were all of lower than BUO group( P 〈0. 05). On day 7 after release of BUO,there was no obvious change in Sham group,and the indexes of BUO_R group and BUO_R﹢EDO group gradually recovered,but they still did not reach the normal level(P〈0. 05). The difference between BUO_R group and BUO_R﹢EDO group was statistically significant(P〈0. 05). The immuno_histochemical results showed that the expression of AQD_1 in collecting duct in BUO group was significantly down_regulated compared with that in Sham group,whereas it was slightly weaker in BUO_R group and BUO_R﹢EDO group than that of Sham group(P〈0. 05). Compared with 3 days after release of BUO,the staining intensity of BUO_R﹢EDO group and BUO_R group was enhanced,but still lower than that of the Sham group. These results were further confirmed by adopting Western blot,and BUO group was also the lowest of the four groups,and BUO_R﹢EDO group was higher than that of BUO group,but lower than that of Sham group( P〈0. 05). Conclusion EDO can promote not only the recovery of AQD_1 protein expression but also the recovery of renal function in young BUO_R rats.

Advance in biomarkers of neuromyelitis optica / 中华实验眼科杂志

Neuromyelitis optica (NMO) is an autoimmune,demyelinating disease of the central nervous system manifesting with optic neuritis and longitudinally extensive transverse myelitis.Aquaporin-4 (AQP4)-IgG is currently regarded as a specific biomarker of NMO.Nevertheless,AQP4-IgG seronegativity in 10％-25％ of NMO patients suggests that there are several other factors involved in NMO immunopathogenesis.In this article,we reviewed current knowledge about biomarkers of NMO from AQP4,myelin-oligodendrocyte glycoprotein,AQP1 and glial fibrillary acidic protein,providing a new insight in the diagnosis of NMO.

Correlations of 18F-FDG PET/CT standardized uptake value, vascular endothelial growth factor, Aquaporin-1 level and clinicopathological features of cervical cancer / 中国医学影像技术

Objective To explore the correlations among standardized uptake value (SUV) and clinicopathological features of cervical cancers,and to observe the association among SUV and expression level of vascular endothelial growth factor (VEGF) and Aquaporin-1 (AQP-1).Methods PET/CT imaging data were analyzed retrospectively in 56 patients with cervical cancer before surgery.The mean SUV (SUV),maximum SUV (SUVmax) and peak SUV (SUVpeak) were measured,and immunohistochemical method was used to detect the expression of VEGF and AQP-1.The relationships of SUV and expression level of VEGF,AQP-1 and clinicopathological features were analyzed.Results SUV SUVpeak and expression level of VEGF and AQP-1 were significantly different in different FIGO stages (all P＜0.05).SUVpeak and expression level of VEGF in tumors with maximum diameter ≥ 4 cm were higher than those in patients with tumors maximum diameter ＜4 cm (both P ＜0.05).SUVpeak and expression level of VEGF and AQP-1 in tumors with cervical stromal invasion depth ≥1/2 were significantly higher than those with cervical stromal invasion depth ＜ 1/2 (all P＜ 0.05).The expression level of VEGF and AQP-1 in patients with lymph node metastasis were higher than those without lymph node metastasis (both P ＜0.05).SUVpeak was correlated with expression level of VEGF (rs =0.529,P＜0.001) and AQP-1 (rs =0.356,P =0.007).Conclusion Preoperative SUVpeak of cervical cancer measured with PET/CT is correlated with clinicopathological features and can be used to guide individual treatment of patients with cervical cancer.

Expression of hypoxia inducible factor-1α and aquaporin-1 in the cornea after alkali burn / 眼科新进展

Objective To detect the expressions of hypoxia inducible factor-1α (HIF-1α) and aquaporin-1 (AQP1) in the alkali-burn cornea and investigate the roles of HIF-1α and AQP1 in alkali-burn mechanisms.Methods Totally 48 healthy adult female Kunming mice were selected,and the left eyes were treated with saline as the control group,and the model of corneal alkali burn was established with concentration of 1 mol · L-1 NaOH on the right eyes,and then these rats were randomly divided into 1-day,4-day,7-day and 14-day group.The expressions of HIF-1α and AQP1 in the cornea were detected using immunofluorescence and qRT-PCR after corneal alkali burn model was successful.Results In the control group,HIF-1 α was expressed in the corneal epithelial basement membrane,but it was increased in the corneal epithelium layer 1 day after alkali burn,and it was expressed in the corneal epithelium layer and stroma 4 days,and peaked 7 days after alkali burn;AQP1 was weakly expressed only in the endothelial layer in the control group,but it was increased in the corneal endothelial layer 1 day after alkali burn,and it was strongly expressed in the endothelial cell layer and the stroma 4 days and 7 days after alkali burn.qRT-PCR indicated that the relative expression level of HIF-1α mRNA was 269.70 ± 15.68 in 1-day group,350.50 ± 67.26 in 4-day group and 272.10 ±6.88 in 7-day group,respectively,which all were higher than that in the control group (188.70 ± 33.99),with significant difference (P ＜ 0.05).In addition,the relative expression level of AQP1 mRNA was 61.90 ± 5.45 in 1-day group and 48.34 ± 1.33 in 7-day group,which were significantly higher than that in the control group (36.43 ± 3.95),with statistical difference (P ＜ 0.05).Conclusion Alkali burn can cause the pathological changes in the cornea,and HIF-1 α and AQP1 involve in corneal injury after alkali burn.

Expression of AQP1 and AQP2 in renal tissue of congenital hydronephrosis and its correlation with glomerular filtration rate / 国际检验医学杂志

Objective To investigate the expression of aquaporin 1(AQP1)and AQP2 in renal tissue of congenital hydronephrosis and its correlation with glomerular filtration rate(GFR).Methods Renal tissue specimens in 43 children cases of pathologically confirmed congenital hydronephrosis and normal kidney tissue specimens in 16 cases of operation were selected as the case group and healthy control group,the Western-blot and reverse transcription polymerase chain reaction were adopted to detect the expression levels of AQP 1, AQP2 protein and gene in the two groups,and its relationship with GFR was analyzed.Results The expres-sion levels of kidney tissue AQP1,AQP2 protein and gene in the case group were significantly lower than those in the healthy control group,the difference was statistically significant(P<0.05);the urine osmolality and GFR level in the case group were significantly lower than those in the healthy control group,while BUN and Scr levels in the case group were higher than those in the healthy control group,the difference was statis-tically significant(P< 0.05);the GFR level in the case group was positively correlated with AQP 1,AQP2 protein and gene expression levels(P<0.01).Conclusion The expression of AQP1 and AQP2 in renal tissue of congenital hydronephrosis is dow n-regulated,moreover is closely related to the disease severity degree.

Effect of ulinastatin pretreatment on expression of aquaporin 1 and 5 in rats with acute lung injury induced by cardiopulmonary bypass / 中华麻醉学杂志

Objective To evaluate the effect of ulinastatin (UT1) on the expression of aquaporin 1 (AQP1) and AQP5 in rats with acute lung injury induced by cardiopulmonary bypass (CPB).Methods Forty-eight clean-grade healthy adult male Sprague-Dawley rats,weighing 200-250 g,were divided into 3 groups (n=16 each) using a random number table method:sham operation group (Sham group),CPB group and UTI group.UTI 200 000 U/kg was injected intravenously at 10 min prior to CPB in UTI group.The model of CPB was established in CPB and UTI groups.The equal volume of normal saline was intravenously injected at 10 min prior to puncture or at 10 min prior to CPB in Sham and CPB groups.Rats were sacrificed,and lung tissues were excised for determination of weight to dry weight ratio (W/D ratio),expression of AQP1 and AQP5 (by immunohistochemistry),expression of AQP1 and AQP5 protein and mRNA (by real-time polymerase chain reaction or Western blot) and for examination of morphological structure (with a light microscope) and ultrastructure of lung tissues (with an electron microscope).Injured alveolar rate (IAR) and rates of AQP1 and AQP5 positive cells were calculated.Results Compared with Sham group,W/D ratio and IAR were significantly increased,rates of AQP1 and AQP5 positive ceils were decreased,and the expression of AQP1 and AQP5 protein and mRNA was down-regulated in CPB and UTI groups (P＜0.05).Compared with CPB group,W/D ratio and IAR were significantly decreased,rates of AQP1 and AQP5 positive cells were increased,and the expression of AQP1 and AQP5 protein and mRNA was up-regulated in UTI group (P＜0.05).The injury to morphological structure and ultrastructure was significantly attenuated in UTI group when compared with CPB group.Conclusion The mechanism by which UTI pretreatment reduces CPB-induced acute lung injury is related to up-regulating the expression of AQP1 and AQP5 in rats.

Advance in biomarkers of neuromyelitis optica / 中华实验眼科杂志

Neuromyelitis optica ( NMO ) is an autoimmune, demyelinating disease of the central nervous system manifesting with optic neuritis and longitudinally extensive transverse myelitis. Aquaporin.4 ( AQP4 ) .IgG is currently regarded as a specific biomarker of NMO. Nevertheless,AQP4.IgG seronegativity in 10％-25％ of NMO patients suggests that there are several other factors involved in NMO immunopathogenesis. In this article,we reviewed current knowledge about biomarkers of NMO from AQP4, myelin.oligodendrocyte glycoprotein, AQP1 and glial fibrillary acidic protein,providing a new insight in the diagnosis of NMO.

Inhibitors of aquaporin 1 and its role in tumor development and progression / 药学学报

Aquaporin 1 (AQP1), the first water channel protein discovered among the aquaporin family, is a hydrophobic transmembrane protein involved in transcellular water movement. Recent evidence shows that AQP1 plays a role in tumor cell proliferation and migration, angiogenesis and tumor development and progression, representing a potential therapeutic target. In this review, we discuss the structures, functions and inhibitors of AQP1, as well as the involvement of AQP1 in tumor development and progression.

Effects of dexmedetomidine on expression of aquaporins 1 and 5 during lung ischemia/reperfusion in rats: an in vitro experiment / 中华麻醉学杂志

Objective To evaluate the effects of dexmedetomidine on the expression of aquaporins 1 (AQP1) and AQP5 during lung ischemia/reperfusion (I/R) in rats in an in vitro experiment.Methods SPF healthy male Sprague-Dawley rats,aged 3-4 months,weighing 250-320 g,were used in this study.Forty-five isolated rat lungs in which the model of isolated lung perfusion was successfully established were divided into 3 groups (n=15 each) using a random number table:sham operation group (S group),I/R group and dexmedetomidine group (D group).The isolated rat lungs were continuously perfused for 150 min in group S.After 15 min of perfusion,the isolated rat lungs were subjected to 60 min of ischemia and apnea followed by 75 min of ventilation and reperfusion to establish the model of isolated lung I/R injury in group I/R.In group D,the isolated rat lungs were perfused for 15 min with K-H perfusion fluid containing 10 nmol/L dexmedetomidine,and then subjected to 60 min of ischemia and apnea followed by 75 min of ventilation and reperfusion with K-H perfusion fluid containing 10 nmol/L dexmedetotnidine.The lung compliance,airway resistance,perfusion flow and partial pressure of arterial oxygen (PaO2) were recorded at 10 min of perfusion and 15,45 and 75 min after restoration of perfusion.Lung tissues were obtained at 75 min after restoration of perfusion for determination of wet/dry weight ratio (W/D ratio) and for examination of the pathological changes and changes in the uhrastructure.The expression of AQP1 and AQP5 protein and mRNA in lung tissues was detected by Western blot and real-time polymerase chain reaction,respectively.Results Compared with S group,the airway resistance was significantly increased and lung compliance,perfusion flow and PaO2 were decreased during reperfusion,and W/D ratio was increased in I/R and D groups (P＜0.05),the expression of AQP1 and AQP5 protein and mRNA in lung tissues was significantly down-regulated in group I/R,and the expression of AQP 1 and AQP5 protein and mRNA in lung tissues was significantly up-regulated in group D (P＜0.05).Compared with I/R group,the airway resistance was significantly decreased and lung compliance,perfusion flow and PaO2 were increased during reperfusion,W/D ratio was decreased,the expression of AQP1 and AQP5 protein and mRNA in lung tissues was up-regulated (P＜0.05),and the pathological changes of lung tissues was significantly attenuated in group D.Conclusion The mechanism by which dexmedetomidine reduces I/R injury may be related to up-regulation of the expression of AQP1 and AQP5 in rats in an in vitro experiment.

Effect of Methylprednisolone on expression of aquaporin 1 in lung tissue of pulmonary edema rats induced by adrenaline / 中华实用儿科临床杂志

Objective To observe the changes in the lung aquaporin 1 (AQP1) expression in adrenaline-induced pulmonary edema(PE),and the effect of Methylprednisolone (MP) on its expression.Methods Fifty Wister rats of 1-month old were randomly divided into 5 groups (10 rats in each group):control,adrenaline PE,MP A,MP B,and MP C groups,respectively.Control group animals were treated with 0.27 mL 9 g/L saline;PE group was given 2.7 mg/kg adrenaline (1 ∶ 1 000) by intraperitoneal injection;MP A,MP B and MP C groups rats were intraperitoneally injected 10 mg/kg,20 mg/kg,and 30 mg/kg MP intraperitoneally immediately after intraperitoneal injection of adrenaline,respectively.The morphology changes in the lungs were observed with HE staining,and lung wet/dry weight (W/D) was measured.The levels of AQP1 mRNA,AQP1 protein,and AQP1 distribution in the lung tissues were detected by using real time-polymerase chain reaction,Western blot,and immunohistochemical method.Results (1)PE group exhibited a faster breathing rate,and double lung volume increased significantly;there was a visible hemorrhagic distribution in the lung surface and cross section,endotracheal filled with white or pink foam liquid.(2) The W/D of rats in PE group was higher than that of the control group (6.50 ± 0.53 vs.4.59 ± 0.36,P ＜ 0.05).(3) Pathological grading of PE group (3.80 ± 0.42) increased significantly compared with that of the MP A group (3.30 ± 0.48),MP B group (2.30 ± 0.68) and MP C group (1.20 ± 0.42),and there were significant differences (all P ＜ 0.05).(4) Immunohistochemistry showed that the expression of AQP1 in PE group (1.20 ± 0.79) was reduced compared with that of the control group (4.20 ± 1.03),and there were significant differences (all P ＜ 0.05).(5) The levels of AQP1 mRNA and AQP1 protein (0.12 ± 0.43 and 0.20 ± 0.04) were significantly lower than those of the control group (0.90 ± 0.32 and 0.60 ± 0.15),and there were significant differences (all P ＜ 0.05);compared with PE group,AQP1 mRNA and AQP1 protein of each group with MP treatment showed the highest values (MP A group:0.17 ±0.06 and 0.32 ±0.04,MP B group:0.39 ±0.13 and 0.37-±0.09,MP C group:0.61 ±0.21 and 0.44 ± 0.07) (all P ＜ 0.05).Conclusion The expression of AQP1 reduced in adrenaline-induced PE rats.MP could improve the expression of AQP1,and significantly ameliorate the PE and bleeding.

Correlation study of the effect of thrombin and hemoglobin on aquaporin and hydrocephalus in rats / 中国脑血管病杂志

Objective To investigate the effect of thrombin and hemoglobin on aquaporin (AQP) and the correlation between AQP and hydrocephalus.Methods Eighty-four clean grade healthy male SD rats were randomly divided into 3 groups:a control group,a thrombin group,and a hemoglobin group using the random number table method.A hydrocephalus model was induced by injecting isotonic saline (0.3 ml),thrombin (0.3 ml[10,U/ml]) and hemoglobin (0.3 ml[150 mg/ml]),respectively into the cisterna magna.According to the deficiency and complement way,each group maintained 24 rats.The relative area of the lateral ventricles,the expression of AQP1 and AQP4,and the correlation between AQP and the area of the lateral ventricles were observed at 1,3,7,and 14 d after molding.Results (1) Compared with the control group,both the thrombin group and hemoglobin group showed hydrocephalus at 1 ,3 ,7 and 14 d,and they were most obvious at 1 day (6.94±0.19% and 6.58±0.15% vs.3.40±0.13%,6.06±0.12% and 5.79±0.09% vs.3.55±0.15%,5.80±0.13% and 5.58±0.08% vs.3.78±0.18%,5.66±0.14% and 5.47±0.13% vs.3.52±0.18 %,respectively).There were significant differences (all P0.05);in the thrombin group and hemoglobin group,compared with those at 1 d,the expression levels of AQP1 and AQP4 at 3,7,and 14 d were significantly decreased (all P<0.01);compared with those at 3 d,AQP1 was decreased significantly at 7 and 14 d (P<0.05).The differences were statistically significant (P<0.05).(3) The relative expression levels of AQP1 (r=0.983,P<0.01) and AQP4 (r=0.987,P<0.01) in the thrombin group at each time point were positively correlated with the contralateral ventricular area;and the relative expression levels of AQP1 (r=0.964,P<0.01) and AQP4 (r=0.962,P<0.01) in the hemoglobin group at each time point were positively correlated with the contralateral ventricular area Conclusions After injecting thrombin and hemoglobin into subarachnoid space,it could cause the increased expression levels of AQP1 and AQP4 of ventricles and their surrounding areas.Thrombin and hemoglobin may be the important mediating factors of hydrocephalus after subarachnoid hemorrhage.

Association between aquaporin 1 and malignant tumors / 国际肿瘤学杂志

Aquaporin1 (AQP1) is a member of a family of specific channel proteins which could mediate the trans-biofilm transportation of small molecules such as water.Recent studies have shown that AQP1 is highly expressed in cancer tissues.It also has an effect on the proliferation and migration of cancer cells, angiogenesis in cancer and so on.AQP1 is expected to be a marker of screening, diagnosis, treatment and prognosis at tumor early stage.

Influence of infusion of mesenchymal stem cells by different routes on the expression of AQP1 and AQP2 in rats with adriamycin-induced nephropathy / 介入放射学杂志

Objective To evaluate the therapeutic effect of bone marrow mesenchymal stem cell (MSC) infusion transplantation via renal artery and via caudal vein in treating chronic kidney disease (CKD) in rats,and to compare the expressions of aquaporin1 (AQP1) and aquaporin2 (AQP2) between the two transplantation routes.Methods A total of 50 male SD rats were selected for this experiment.Two experimental rats were used to make preparation of bone marrow MSC.CKD model was established with infusion of adriamycin via caudal vein in 36 rats.The 36 CKD models were randomly divided into adriamycininduced renal failure model control group (A-C group,n=12),MSC transplantation through the right renal artery group (M-A group,n=12) and MSC transplantation through the caudal vein group (M-V group,n=12).The remaining 12 male SD rats were used as the blank control group (N group).One week after the last bone marrow MSC transplantation,the 24 h urine volume,24 h urinary protein content,serum sodium content and serum albumin level were measured,and AQP1 and AQP2 expressions in the kidney tissue were determined by immunohistochemistry.Results Compared with A-C group,the serum albumin level and 24h urine volume in both M-V group and M-A group were significantly increased (P＜0.05),while 24h urinary protein content and serum sodium content were remarkably decreased (P＜0.05).The 24h urinary protein content in the M-A group was obviously lower than that in the M-V group (P＜0.05).The AQP1 and AQP2 expressions in the kidney tissue in both M-V group and M-A group were strikingly lower than those in the A-C group (P＜ 0.05),but no statistically significant differences in AQP1 and AQP2 expressions existed between the M-V group and the M-A group (P＞0.05).Conclusion MSC transplantation can increase serum albumin,and lower urinary protein,serum sodium and the expressions of AQP1 and AQP2 in renal parenchymal cells,which has the effect on repairing renal injury of adriamycin-induced CKD rats.For a given period of time,the clinical curative effect of MSC transplantation via renal artery is better than that of MSC transplantation via peripheral vein,but the difference in curative effect between the two MSC transplantation pathways has no obvious correlation with AQP1 and AQP2 expressions.