2.Effect of vasoactive intestinal peptide on defecation and VIP-cAMP-PKA-AQP3 signaling pathway in rats with constipation.
Yongxue ZHOU ; Yujin WANG ; Hong ZHANG ; Shuguang YAN ; Bin WANG ; Pei XIE
Journal of Central South University(Medical Sciences) 2016;41(11):1175-1180
To observe the effect of vasoactive intestinal peptide (VIP) on the metabolism of intestinal fluid and cyclic AMP protein kinase A signaling pathway (cAMP-PKA) and water channel protein 3 (AQP3) in rats with constipation, and to explore the mechanism of VIP in the treatment of constipation.
Methods: A total of 45 healthy adult rats were randomly divided into a control group, a model group, a model +VIP group. After 4 weeks of VIP treatment, the first black stool time were examined with the ink gastric method; the water content in feces was calculated; the morphological changes in colonic tissues were observed by HE staining. The expression of VIP and AQP3 protein levels in colon tissues were detected by Western blot; and the cAMP, PKA, AQP3 mRNA expression levels were detected by quantitative real time polymerase chain reaction (qPCR).
Results: Compared with the control group, the first black stool time was prolonged, the water content of fecal decreased significantly (both P<0.01); part of the colon mucosa epithelial cells were destructed; the goblet cell volume decreased and quantity was reduced; the contents of AQP3 and VIP in colon tissues were significantly decreased, and the cAMP, PKA and AQP3 mRNA levels were decreased in the model group (all P<0.05). Compared with the model group, the first black stool time in the model +VIP group was shortened, the fecal water content increased significantly (both P<0.05); the mucosal epithelium integrity improved, the number of goblet cells increased; the content of AQP3 and VIP in colon tissues was increased, and the cAMP, PKA, and AQP3 mRNA levels were elevated (all P<0.05).
Conclusion: Intravenous injection of VIP can regulate intestinal fluid metabolism and improve the symptoms of constipation in rats, which might be related to the regulation of VIP-cAMP-PKA-AQP3 signaling pathway.
Animals
;
Aquaporin 3
;
physiology
;
Aquaporins
;
Blotting, Western
;
Colon
;
chemistry
;
pathology
;
Constipation
;
physiopathology
;
therapy
;
Cyclic AMP
;
physiology
;
Defecation
;
Epithelial Cells
;
pathology
;
Feces
;
chemistry
;
Goblet Cells
;
pathology
;
Intestinal Mucosa
;
metabolism
;
pathology
;
RNA, Messenger
;
Rats
;
Signal Transduction
;
Vasoactive Intestinal Peptide
;
administration & dosage
;
physiology
;
therapeutic use
3.Relationship between efficacy exertion of diuretic traditional Chinese medicines and aquaporin.
Peng-cheng WANG ; Shan ZHAO ; Qiu-hong WANG ; Hai-xue KUANG
China Journal of Chinese Materia Medica 2015;40(12):2272-2277
In recent years, the discovery and studies on aquaporin have made us have a more in-depth understanding about the physiological and pathological processes of water metabolism. Over years, however, there has been no quantitative study on the target sites of diuretic traditional Chinese medicines at the molecular level. In that case, aquaporin was found to been a new target molecule to explain the efficacy exertion of diuretic traditional Chinese medicines. By studying aquaporin, researchers can understand the implicit meaning of the diuretic effect of traditional Chinese medicines and conduct quantitative studies on the diuretic effect. So far, many scholars have conducted a series of studies in the traditional Chinese medicine field by using the findings on aquaporin and made certain advances. This article provides a summary about the efficacy exertion of diuretic traditional Chinese medicines through target molecule aquaporin.
Animals
;
Aquaporins
;
genetics
;
metabolism
;
Diuretics
;
pharmacology
;
Drugs, Chinese Herbal
;
pharmacology
;
Humans
;
Medicine, Chinese Traditional
;
Water
;
metabolism
4.Agmatine Attenuates Brain Edema and Apoptotic Cell Death after Traumatic Brain Injury.
Jae Young KIM ; Yong Woo LEE ; Jae Hwan KIM ; Won Taek LEE ; Kyung Ah PARK ; Jong Eun LEE
Journal of Korean Medical Science 2015;30(7):943-952
Traumatic brain injury (TBI) is associated with poor neurological outcome, including necrosis and brain edema. In this study, we investigated whether agmatine treatment reduces edema and apoptotic cell death after TBI. TBI was produced by cold injury to the cerebral primary motor cortex of rats. Agmatine was administered 30 min after injury and once daily until the end of the experiment. Animals were sacrificed for analysis at 1, 2, or 7 days after the injury. Various neurological analyses were performed to investigate disruption of the blood-brain barrier (BBB) and neurological dysfunction after TBI. To examine the extent of brain edema after TBI, the expression of aquaporins (AQPs), phosphorylation of mitogen-activated protein kinases (MAPKs), and nuclear translocation of nuclear factor-kappaB (NF-kappaB) were investigated. Our findings demonstrated that agmatine treatment significantly reduces brain edema after TBI by suppressing the expression of AQP1, 4, and 9. In addition, agmatine treatment significantly reduced apoptotic cell death by suppressing the phosphorylation of MAPKs and by increasing the nuclear translocation of NF-kappaB after TBI. These results suggest that agmatine treatment may have therapeutic potential for brain edema and neural cell death in various central nervous system diseases.
Active Transport, Cell Nucleus/drug effects
;
Agmatine/*therapeutic use
;
Animals
;
Apoptosis/*drug effects
;
Aquaporins/metabolism
;
Blood-Brain Barrier/physiopathology
;
Brain Edema/*drug therapy
;
Brain Injuries/*pathology
;
Male
;
Mitogen-Activated Protein Kinases/metabolism
;
Motor Cortex/*pathology
;
NF-kappa B/metabolism
;
Phosphorylation/drug effects
;
Rats
;
Rats, Sprague-Dawley
5.Effects of electroacupuncture on cochlea morphology and expression of aquaporins in guinea pigs with endolymphatic hydrops.
Liyuan JIANG ; Canjun WANG ; Fangying NI ; Huade CHEN
Chinese Acupuncture & Moxibustion 2015;35(6):579-584
OBJECTIVETo observe the effects of electroacupuncture (EA) on cochlea morphology and expression of aquaporin 1 (AQP1) in guinea pigs with endolymphatic hydrops, so as to explore the possible mechanism of EA on endolymphatic hydrops.
METHODSForty guinea pigs were randomly divided into a blank group, a model group, a medication group and an EA group, 10 guinea pigs in each one. Model of endolymphatic hydrops was established by using intraperitoneal injection of aldosterone. Guinea pigs in the blank group and model group were treated with identical immobilization as EA group but no treatment was given; guinea pigs in the medication group were treated with intragastric administration of hydrochlorothiazide at a dose of 5 mg/kg, once a day for consecutive 10 days; guinea pigs in the EA group were treated with' EA at "Baihui" (GV 20) and "Tinggong"(SI 19), once a day for consecutive 10 days. The serum ionic concentration in each group was tested by turbidimetric method; hematoxylin-eosin staining was used to measure the severity of cochlea hydrops; immunohistochemical method was used to observe the expression of AQP1 in the cochlea.
RESULTS(1) There was no endolymphatic hydrops in the blank group, moderate-severe endolymphatic hydrops in the model group and slight endolymphatic hydrops in the EA group and medication group. (2) The concentration of K+ and Ca2+ in the EA group was higher than that in the model group and medication group (all P<0. 01); the concentration of Na+ was lower than that in the model group (P< 0. 01) but higher than that in the medication group (P<0. 01); the concentration of Cl- was higher than that in the medication group (P<0. 01), but not significantly different from the model group (P>0. 05). (3) The ratio of expression area of AQP1 in the model group was lower than that in the blank group (P<0. 01); the ratio of expression area of AQP1 in the EA group was higher than that in the model group (P<0. 01), and lower than that in the medication group without significant difference (P>0. 05).
CONCLUSIONEA could relieve the endolymphatic hydrops in guinea pigs; the mechanism is likely to be related with up-regulating the expression of AQP1 in cochlea and ion concentration might be an important factor involved.
Animals ; Aquaporins ; genetics ; metabolism ; Cochlea ; anatomy & histology ; metabolism ; Disease Models, Animal ; Electroacupuncture ; Endolymphatic Hydrops ; genetics ; metabolism ; therapy ; Guinea Pigs ; Humans ; Male
6.Expressions of aquaporins decrease in the prostate and seminal vesicles of castrated rats.
Jun JIANG ; Jin-cheng TIAN ; Ji-yi XIA ; Yong-sheng ZHU ; Rui JIANG
National Journal of Andrology 2015;21(4):300-307
OBJECTIVETo investigate the levels of secretions from the prostate and seminal vesicles and their association with the expressions of aquaporins (AQP) in the prostatic tissue and seminal vesicles of castrated rats.
METHODSWe randomly divided 18 eight-week-old male SD rats into a control, a castration, and a testosterone (T) replacement group. Four weeks after surgical castration, we detected the plasma T level and measured the volumes of the secretions and the expressions of AQPs 3, 7, and 10 - 12 in the prostate and seminal vesicles of the rats.
RESULTSThe plasma T level was significantly lower in the castrated models ([30. 98 ± 28. 84] ng/dl) than in the rats of the control ([700.78 ± 123.8] ng/dl) and T replacement groups ([688.08 ± 132. 47] ng/dl) (P <0. 05). The castration group, in comparison with the control and T replacement groups, showed remarkably reduced ratios of prostatic secretion volume / prostate weight ([11.1 ± 0.30] vs [2.32 ± 0.61] and [2.13 ± 0.56] %, P <0. 05) and seminal vesicle secretion volume / seminal vesicle weight ( [4. 78 ± 1. 97 ] vs [57. 36 ± 11. 86] and [55. 74 ± 7. 21] %, P < 0. 05). Immunohistochemistry revealed the expressions of AQPs 3 and 7 in the epithelial envelop and cytoplasm and that of AQP 11 the in endothelial envelop and cytoplasm of the prostate and seminal vesicles. Western blot exhibited significantly lower expressions of AQPs 3, 7, and 10 - 12 in the prostate and seminal vesicles of the castrated rats than in the animals of the control and T replacement groups (P <0. 05).
CONCLUSIONSignificant decreases of the secretions from the prostate and seminal vesicles may be related to the reduced expressions of AQPs 3, 7, and 10 - 12 in the prostatic tissue and seminal vesicles in castrated rats.
Animals ; Aquaporins ; metabolism ; Humans ; Male ; Orchiectomy ; Prostate ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Seminal Vesicles ; metabolism ; Testosterone ; blood
7.H₂S protecting against lung injury following limb ischemia-reperfusion by alleviating inflammation and water transport abnormality in rats.
Qi Ying Chun QI ; Wen CHEN ; Xiao Ling LI ; Yu Wei WANG ; Xiao Hua XIE
Biomedical and Environmental Sciences 2014;27(6):410-418
OBJECTIVETo investigate the effect of H₂S on lower limb ischemia-reperfusion (LIR) induced lung injury and explore the underlying mechanism.
METHODSWistar rats were randomly divided into control group, IR group, IR+ Sodium Hydrosulphide (NaHS) group and IR+ DL-propargylglycine (PPG) group. IR group as lung injury model induced by LIR were given 4 h reperfusion following 4 h ischemia of bilateral hindlimbs with rubber bands. NaHS (0.78 mg/kg) as exogenous H₂S donor and PPG (60 mg/kg) which can suppress endogenous H₂S production were administrated before LIR, respectively. The lungs were removed for histologic analysis, the determination of wet-to-dry weight ratios and the measurement of mRNA and protein levels of aquaporin-1 (AQP₁), aquaporin-5 (AQP₅) as indexes of water transport abnormality, and mRNA and protein levels of Toll-like receptor 4 (TLR₄), myeloid differentiation primary-response gene 88 (MyD88) and p-NF-κB as indexes of inflammation.
RESULTSLIR induced lung injury was accompanied with upregulation of TLR₄-Myd88-NF-κB pathway and downregulation of AQP1/AQP₅. NaHS pre-treatment reduced lung injury with increasing AQP₁/AQP₅ expression and inhibition of TLR₄-Myd88-NF-κB pathway, but PPG adjusted AQP₁/AQP₅ and TLR4 pathway to the opposite side and exacerbated lung injury.
CONCLUSIONEndogenous H₂S, TLR₄-Myd88-NF-κB pathway and AQP₁/AQP₅ were involved in LIR induced lung injury. Increased H₂S would alleviate lung injury and the effect is at least partially depend on the adjustment of TLR₄-Myd88-NF-κB pathway and AQP₁/AQP₅ expression to reduce inflammatory reaction and lessen pulmonary edema.
Acute Lung Injury ; complications ; pathology ; prevention & control ; Animals ; Aquaporins ; metabolism ; Drug Evaluation, Preclinical ; Edema ; etiology ; pathology ; Hydrogen Sulfide ; pharmacology ; therapeutic use ; Inflammation ; prevention & control ; Lung ; pathology ; Male ; Myeloid Differentiation Factor 88 ; metabolism ; NF-kappa B ; metabolism ; Random Allocation ; Rats ; Rats, Wistar ; Reperfusion Injury ; complications ; pathology ; prevention & control ; Toll-Like Receptor 4 ; metabolism ; Water ; metabolism
8.Expression and significance of aquaporin-9 in the liver.
Journal of Central South University(Medical Sciences) 2014;39(8):868-873
Aquaporin-9 (AQP9) is a membrane-span transport protein expressed in the liver. It is located in the cytoplasm membrane of hepatic cells. In addition to water, it is also permeable to glycerol, urea, and other small solutes. Several evidences have revealed that AQP9 is involved in multiple physiological and pathological process of the liver. This paper summarized the expression of AQP9 in the liver and the effect on the physiological and pathological processes of the liver. AQP9 may be defined as a novel target for diagnosis and treatment of hepatic diseases.
Aquaporins
;
metabolism
;
Cell Membrane
;
metabolism
;
Glycerol
;
Hepatocytes
;
metabolism
;
Humans
;
Liver
;
metabolism
;
Urea
9.Time-Dependent Expression Patterns of Cardiac Aquaporins Following Myocardial Infarction.
Hong Zhe ZHANG ; Moo Hyun KIM ; Ju Hyun LIM ; Hae Rahn BAE
Journal of Korean Medical Science 2013;28(3):402-408
Aquaporins (AQPs) are expressed in myocardium and the implication of AQPs in myocardial water balance has been suggested. We investigated the expression patterns of AQP subtypes in normal myocardium and their changes in the process of edema formation and cardiac dysfunction following myocardial infarction (MI). Immunostaining demonstrated abundant expression of AQP1, AQP4, and AQP6 in normal mouse heart; AQP1 in blood vessels and cardiac myocytes, AQP4 exclusively on the intercalated discs between cardiac myocytes and AQP6 inside the myocytes. However, neither AQP7 nor AQP9 proteins were expressed in CD1 mouse myocardium. Echocardiography revealed that cardiac function was reduced at 1 week and recovered at 4 weeks after MI, whereas myocardial water content determined by wet-to-dry weight ratio increased at 1 week and rather reduced below the normal at 4 weeks. The expression of cardiac AQPs was up-regulated in MI-induced groups compared with sham-operated control group, but their time-dependent patterns were different. The time course of AQP4 expression coincided with that of myocardial edema and cardiac dysfunction following MI. However, expression of both AQP1 and AQP6 increased persistently up to 4 weeks. Our findings suggest a different role for cardiac AQPs in the formation and reabsorption of myocardial edema after MI.
Animals
;
Aquaporin 1/metabolism
;
Aquaporin 4/metabolism
;
Aquaporin 6/metabolism
;
Aquaporins/*metabolism
;
Edema/pathology
;
Immunohistochemistry
;
Mice
;
Muscle Cells/metabolism
;
Myocardial Infarction/*metabolism/pathology/ultrasonography
;
Myocardium/metabolism/pathology
;
Time Factors
10.Progress on the application of aquaporins in Chinese medicine.
Xing LIANG ; Wei MAO ; Xu-Sheng LIU
Chinese journal of integrative medicine 2013;19(7):556-559
Aquaporins are a group of membrane proteins, which are known as the passages of water molecules transforming through the biological membrane lipid bilayer and distributing in almost all of the organs and tissues of living creatures. Aquaporins play important roles in maintaining water balance and internal environment stability. As a new entry point, aquaporins are involved in the researches on water metabolism, physiological regulation and pathological essence in viscera-state more and more widely in recent years. The literature on traditional Chinese medical studies, which related to aquaporins and were published in the last decade, was reviewed and the progress on application of aquaporin in Chinese medicine was summarized in this paper.
Aquaporins
;
metabolism
;
Humans
;
Kidney
;
pathology
;
Medicine, Chinese Traditional
;
Syndrome
;
Viscera
;
pathology

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