Effects of a Topical Anti-aging Formulation on Skin Aging Biomarkers.

Objective: Following previous clinical trials, an antiaging product (Restorative Skin complex [RSC]; Alastin Skin Care Carlsbad, a Galderma company), was investigated for its effects on Klotho gene regulation, telomere length, and histological biopsy changes to provide a comprehensive picture of the mechanism and efficacy of its anti-aging effect. Methods: Neonatal human fibroblasts were used for telomere length studies to examine the effect of the full RSC formulation and the amino acid components Tripeptide-1 and Hexapeptide-12 (TriHex™) on these cellular aging mechanisms. In addition, RNA sequencing was conducted using human keratinocytes specifically investigating Klotho and related genes. This was supplemented by a clinical study using biopsy samples. Results: TriHex™ significantly upregulated the Klotho gene and related FGF23, FGFR1 and FOXO3B anti-aging genes. Significant telomere shortening reduction over control was demonstrated with the RSC formulation at four weeks and with TriHex™ at six weeks for all percentiles tested. Previous clinical studies demonstrated that the use of the antiaging regimen for 12 weeks produced a statistically significant improvement in scores for all evaluated parameters. Restaining of previous biopsy blocks from the clinical trial revealed positive ECM changes, stimulation of collagen, fibrillin, CD44 and elastin. Limitations: The study was limited by a relatively small numbers of patients in the clinical trial and the non-competitive nature of the trial. Conclusion: RSC anti-aging formulation and its TriHex™ components demonstrated significant reduction in telomere shortening, upregulation of Klotho and FOXO3 genes and biopsy validation of anti-aging efficacy. This new science supplements previous trials that demonstrated clinical efficacy of the formulation.

Effect of resveratrol on the repair of kidney and brain injuries and its regulation on klotho gene in d-galactose-induced aging mice.

Resveratrol is a natural polyhydroxy trans-stilbene product with many biological activities. One of the most striking biological activities of it is its anti-aging potential. Resveratrol can exhibit anti-aging activity via a variety of signaling pathways, however, the repair effect of it on kidney and brain injury in aging mice induced by d-galactose and its regulation on klotho gene expression have not been reported. Herein, the anti-aging activity of resveratrol and its effect on the repair of kidney and brain injuries in d-galactose-induced aging mice, as well as its regulation of klotho gene expression in these two tissues were investigated. The results indicated that resveratrol could significantly increase the aged cell viability and improve the pathological status of aging mice via inhibiting the formation of malondialdehyde and enhancing the activities of superoxide dismutase and catalase. The histological analysis suggested that resveratrol could remarkably repair the damages of kidney and brain tissues in aging mice. Moreover, PCR and western blot have shown that resveratrol could obviously increase the anti-aging klotho gene expression in the above tissues. The data in this paper further revealed and enriched the anti-aging mechanism of resveratrol, and the methods established in this study can be used as a tool to evaluate the anti-aging activity of drugs to a certain extent.

The predictive value of Klotho polymorphism, in addition to classical markers of CKD-MBD, for left ventricular hypertrophy in haemodialysis patients.

PURPOSE: Cardiovascular events are the major reasons for mortality in haemodialysis patients. Fibroblast growth factor 23 (FGF23), Klotho protein and G-395A Klotho gene polymorphism have been associated with effects on the cardiovascular system. Our study investigates the interrelationship between Klotho protein gene variations, mineral-bone metabolism and left ventricular hypertrophy in patients undergoing chronic haemodialysis programme. MATERIALS AND METHODS: Patients (n = 142) were genotyped for G-395A Klotho gene. Components of mineral-bone metabolism, classical and non-classical (FGF23, Klotho and vitamin D) as well as echocardiographic examination were determined. Predictive models were designed to determine the significance of Klotho gene variations and mineral-bone metabolism components for left ventricle hypertrophy (LVH). RESULTS: A-allele carriers were longer on haemodialysis (p = 0.033), and had higher phosphorus levels (p = 0.016) while the level of Klotho protein was significantly lower (p = 0.001) compared to non-A-allele carriers. The best gains were achieved upon addition of allele A, and all three new markers; the AUC made significant improvement from 0.596 to 0.806 (p < 0.001), and improved net reclassification for 82.1% (95% CI 42.9-121.3%). CONCLUSIONS: The genetic background of A-allele carriers of the G-395A Klotho gene polymorphism increases the susceptibility patients to haemodialysis. A-allele carriers are at a higher risk for the development of cardiovascular complications. The addition of non-classical to classical mineral metabolism components improves prediction power to LVH.

Clinical significance of serum and tissue klotho levels in human pancreatic cancer / 中华胰腺病杂志

Objective To investigate the correlation of clinicopathological parameters and prognosis with serum and pancreatic cancer tissue klotho. Methods Immunohistochemistry EnVision two step method was used to assess klotho protein expression of a tissue microarray ( TMA) of 79 pairs of pancreatic tissue and normal surrounding tissue. The serum klotho levels in 39 pancreatic cancer patients and 39 healthy controls who had matched clinical data were measured by ELISA. The relationships between the expression of klotho and the clinicopathological features and survival were analyzed. Results Klotho expression positivity in pancreatic cancer tissue was significantly higher than that in adjacent normal tissues (59. 5％ vs 96. 3％);serum level of klotho was markedly higher in pancreatic cancer patients than that in control group [(670. 30 ± 82. 24)pg/ml vs (310.35 ± 34.65) pg/ml], and both the difference was statistically significant (P<0.001). Klotho expression was negatively associated with tumor clinical stage and lymph node metastasis (P<0. 05), and the expression of klotho did not correlate with patients' gender, age, tumor size, location, local invasion depth and the like. The median survival time in pancreatic cancer patients with positive klotho expression were longer than that in in pancreatic cancer patients with negative klotho expression [(48. 31 ± 6. 94) months vs (19. 50 ±6. 78)months], and the difference was statistically significant (P<0. 01). ROC analysis on serum klotho gave a cutoff value of 376. 51 pg/ml to diagnosis pancreatic cancer with a sensitivity of 84. 6％ and specificity of 87. 2％. Conclusions Klotho level in serum and tissue of pancreatic cancer patients was closely correlated with clinicopathological parameters and prognosis, which may be a potential biomarker for pancreatic cancer.

The role of the ßKlotho gene in uterine endometrial cancer.

OBJECTIVES: Endometrial cancer is the most common cancer of the female genital organs in developed countries, accounting for approximately 50% of all gynecological cancers. The Klotho gene was discovered in 1997 as an anti-aging gene that, when overexpressed, may extend the lifespan, but when disrupted, may be a factor responsible for premature aging syndrome. The aim of the study is to assess the relationship between the clinical and pathological features of endometrial cancer and ßKlotho gene expression. MATERIAL AND METHODS: The expression of ßKlotho gene was studied in 138 cases of endometrioid endometrial carcinoma specimens using Real Time PCR reaction in RNA isolated tissue samples by commercial tests. The expression profile was correlated with the clinicopathological characteristics of endometrial carcinoma. The chi-square independence test and Fisher's test for four-field tables were used to assess the statistical significance of the observed relationships. RESULTS: Significant relationships were found between ßKlotho gene expression and FIGO clinical stage, the degree of histological differentiation and the presence of metastases in the lymph nodes. Higher levels of gene expression correlate with lower degrees of clinical staging according to FIGO, the presence of highly-differentiated endometrial cancer (G1) and the absence of lymph node metastases. CONCLUSIONS: The ßKlotho gene expression might be involved in endometrioid endometrial cancer tumorgenesis. The ßKlotho may in future be used as an useful indicator for endometrial cancer, although further studies are needed.

Studies on the anti-aging activity of a glycoprotein isolated from Fupenzi (Rubus chingii Hu.) and its regulation on klotho gene expression in mice kidney.

In this study, a novel glycoprotein with molecular weight of 22.0 kDa was isolated and purified from Fupenzi (a kind of unripe fruits of Rubus chingii Hu.) by means of anion-exchange (DEAE-52) and gel column chromatography (Sephadex G-100). The glycoprotein consists of a carbohydrate component (81.42 ±â€¯0.96%) and protein component (14.56 ±â€¯1.21%). The anti-aging capability was measured in d­galactose induced aging mice model, and the experimental data showed that the glycoprotein could significantly inhibit the formation of malondialdehyde (MDA) and raise the activities of superoxide dismutase (SOD) and catalase (CAT) in mice kidney and serum. The reverse transcription polymerase chain reaction (RT-PCR), quantitative real time polymerase chain reaction (Q-PCR) and western blots showed that the glycoprotein significantly increase the expression of anti-aging gene klotho in mice kidney. The results suggested that the anti-aging mechanism of FPZ might be achieved by improving the klotho gene expression and repairing the renal function. This study will provide a scientific basis for the view of traditional Chinese medicine that tonifying kidney is the basic way of anti-aging. In addition, the glycoprotein could be exploited as a potent dietary supplement to attenuate aging and prevent age-related diseases in humans.

Hearing analysis in heterozygous and homozygous klotho gene deficient mice.

OBJECTIVE: To understand the crucial role of the klotho gene in hearing development in mouse models. METHODS: PCR was used to identify CBA mice with different genotypes, i.e. WT, heterozygous (klotho +/-) or homozygous (klotho -/-). Mice phenotype and weight were recorded postnatal 25 days (P-25) and auditory brainstem responses (ABR) were used to determine auditory function at P-60. RESULTS: klotho -/- mice tended to have smaller size, lighter weight and higher ABR thresholds at P-60, showing early onset age-related hearing loss (ARHL). CONCLUSION: Heterozygous and homozygous klotho deficient mice exhibit different degrees of hearing loss at young age, with homozygous mice (klotho -/-) showing more severe hearing loss. Our results indicate that persisted expression of klotho protein in the inner ear may potentially delay the onset of ARHL and play an important role in the protection of auditory function.

Relationship between Klotho gene and growth axis GH-IGF1 / 国际儿科学杂志

Klotho was first discovered as an aging-suppressor gene. Klotho protein is highly expressed in the brain and the kidney,but can also serve as a circulating hormone. Evidences suggest that Klotho is involved in calcium phosphate homeostasis,energy metabolism,protection of the cardiovascular system,protection of kid-ney and anti-aging through membrane receptors and hormone-like effects. Currently available studies support a tight interaction between Klotho and the GH-IGF1 axis,with a complex reciprocal regulation between them. On one hand,increased activity of the GH-IGF1 axis upregulates serum Klotho levels,which in turn inhibits the pe-ripheral activity of IGF1,thus forming a negative feedback loop. On the other hand,klotho abrogates the inhibito-ry effect of IGF1 in the pituitary,leading to enhanced GH secretion and further increase of IGF1 production,thus forming a positive feedback loop. In addition,Klotho plays an important role in calcium- phosphate metabolism together with GH-IGF1 and FGF23. In this paper,the regulation of Klotho expression and its relationship with GH-IGF1 axis and mineral metabolism are reviewed briefly.

Correlation between KLOTHO gene and mild cognitive impairment in the Uygur and Han populations of Xinjiang.

The secretive Klotho protein is an anti-aging regulatory hormone that plays a physiological role in many target organs. The present study aims to investigate the correlation between Klotho gene and mild cognitive impairment (MCI) in Uygur and Han populations in Xinjiang. From July 2008 to April 2014, stratified random multistage cluster sampling was used in combination with the methods of on-site questionnaire and household survey to conduct a cross-sectional MCI investigation on selected Uygur and Han subjects aged over 60 years old in Xinjiang region. 323 Uygur and Han MCI patients were randomly selected and matched with 343 subjects in the normal control group. SNaPshot technique was used to detect the polymorphisms of Klotho gene. A case-control associated analysis was conducted to analyze the genotype and allele frequencies of single nucleotide polymorphisms (SNPs) in the MCI group and the normal control group. The polymorphisms of rs1207568 and rs9536314/rs9527025 loci in Klotho gene were different among MCI populations in Xinjiang, and after group assignments based on ethnic background, the polymorphisms of rs1207568 and rs9536314/rs9527025 loci were associated with the Uygur MCI population and were not relevant to the Han MIC population. The frequencies of mutational alleles of rs9536314/rs9527025 locus in the Uygur population were significantly higher than those in the Han population. The genotype and allele frequencies of rs1207568 locus in the Uygur and Han populations were similar. The polymorphisms of rs1207568 and rs9536314/rs9527025 loci in Klotho gene may be associated with the Uygur MCI population in Xinjiang.

The Expressions of Klotho Family Genes in Human Ocular Tissues and in Anterior Lens Capsules of Age-Related Cataract.

PURPOSE: Klotho genes are expressed in limited tissues and have been found to be a pathogenic factor of age-related diseases in mammals, but their expressions and functions in human eyes are yet to be defined. This study was performed to investigate the expression of Klotho family genes in human ocular tissues and anterior lens capsules of age-related cataract. METHODS: Individual tissues were isolated from human eyeballs collected from Henan Eye Bank. Human anterior lens capsules were collected from cortical cataract patients during phacoemulsification with the informed consent. Real-time quantitative reverse transcription was performed to detect the mRNA expressions of α-Klotho, ß-Klotho, γ-Klotho, IGFR1, AKT, and ERK; Western blot analysis for detecting the expression of ERK1/2 and phosphor-ERK1/2 protein; and Pearson correlation analysis was performed to detect the relationship between Klotho genes and IGFR1, AKT or ERK genes. RESULTS: The expressions of α-, ß-, and γ-Klotho mRNA were detected in human retina and optic nerve, but were not detected in iris, ciliary body, sclera, and choroid. Only α-and γ-Klotho mRNA expressions were detected in the lens, and the expression levels were higher than that in the retina and optic nerve. The mRNA expressions of IGFR1 and AKT were not changed among the transparent and the opaque lens capsules. The mRNA expression of ERK was significantly decreased in the opaque lens capsule. Correlation analysis showed that the ERK mRNA expression was positively correlated with the expression of the γ-Klotho gene. Western blot results showed a significant decrease of ERK1/2 and phosphor-ERK1/2 protein in opaque lens capsules. CONCLUSIONS: α- and γ-Klotho genes express in the human retina, optic nerve, and lens. The ß-Klotho gene expresses only in retina and optic nerve. The γ-Klotho gene may regulate human lens epithelial cells' function mainly by the MAPK/ERK1/2 signaling pathway.

Association of KL gene G-395A polymorphisms with coronary heart disease and serum cystatin C level in the elderly Chinese Han population in central China / 重庆医学

Objective To investigate the single nucleotide polymorphism at G-395A site of the Klotho (KL) gene and to analyze its correlation with the coronary heart disease(CHD) and serum Cystatin C(Cys C) level in the elderly Chinese Han population in central China.Methods A case-control study was conducted in 278 elderly Chinese Han population in this department,who were divided into CHD group(138 cases)and control group(140 cases) according to bear angiography coronary or not.G-395A polymorphism of KL gene was determined by TaqMan Gene probe method,and the relationship between G-395A polymorphism and coronary heart disease and serum Cys-C level was analyzed.Results Compared with the control group,the frequency of GG genotype of G-395A in CHD group was significantly higher,and the frequency of AA genotype and AG genotype was not statistically significant.The levels of Cys-C in the GG genotype were higher than those in the AA and AG genotypes both in the control group and coronary heart disease group.Conclusion In the elderly Han population in central China,the risk of suffering coronary heart disease is higher among the GG genotype of the G-395A locus of the KL gene.KL gene G-395A site gene mutation may affect the development of atherosclerosis by affecting blood Cys-C levels.

Klotho, the Holy Grail of the kidney: from salt sensitivity to chronic kidney disease.

The Klotho gene displays an extremely shortened life span with loss of function missense mutations leading to premature multiple organ failure, thus resembling human premature aging syndromes. The transmembrane form of Klotho protein functions as an obligatory co-receptor for FGF23. Klotho and FGF23 are crucial components for the regulation of vitamin D metabolism and subsequently blood phosphate levels. The secreted Klotho protein has multiple regulatory functions, including effects on electrolyte homeostasis, on growth factor pathways as well as on oxidative stress, which are currently the object of extensive research. Klotho protein deficiency is observed in many experimental and clinical disease models. Genetic polymorphisms such as the G-395A polymorphism in the promoter region of the Klotho gene have been associated with the development of essential hypertension. The kidneys are the primary site of Klotho production, and renal Klotho is decreased in CKD, followed by a reduction in plasma Klotho. Klotho deficiency has been both associated with progression of CKD as well as with its cardinal systemic manifestations, including cardiovascular disease. Thus, Klotho has been suggested both as a risk biomarker for early detection of CKD and additionally as a potential therapeutic tool in the future.

G-395A polymorphism in the promoter region of the KLOTHO gene associates with reduced cognitive impairment among the oldest old.

This study aimed to examine the possible association between G-395A polymorphism in the promoter region of the KLOTHO gene and cognitive impairment among Chinese nonagenarians and centenarians. This study is a secondary analysis of the Project of Longevity and Aging in Dujiangyan (PLAD) study. Community-dwelling Chinese people aged 90 years or older were included. G-395A (rs1207568) genotyping in the promoter region of the KLOTHO gene was performed using the TaqMan allelic discrimination assay. Cognitive function was assessed with the mini-mental status examination (MMSE). A total of 706 participants (68.0 % female; mean age 93.5 ± 3.6 years) were included. The KLOTHO G-395A polymorphism genotype frequencies for the whole sample were 2.0 % AA, 30.3 % GA, and 67.7 % GG. The GG genotype frequencies for the cognitive impairment and control groups were 70.2 and 62.7 %, respectively. Cognitive impairment prevalence was significantly lower in the GA+AA group than in the GG genotype group (61.4 vs. 69.0 %, p = 0.044). GA+AA genotype subjects had a significantly lower risk of cognitive impairment (odds ratio 0.66; 95 % confidence interval 0.44 to 0.98) than GG genotype individuals after adjusting for age, gender, and other relevant risk factors. KLOTHO G-395A polymorphism associates with reduced cognitive impairment in a sample of Chinese nonagenarians and centenarians.

FGF-23, α-Klotho Gene Polymorphism and Their Relationship with the Markers of Bone Metabolism in Chronic Peritoneal Dialysis Patients.

OBJECTIVE: The aim of the present study was to evaluate the variations of some major bone metabolism markers with reference to klotho gene polymorphism (KGP) and bone mineral density (BMD) values in patients on chronic peritoneal dialysis (CPD). MATERIALS AND METHODS: In 51 CPD patients and 40 healthy persons, assays for intact parathormone (iPTH), fibroblast growth factor 23 (FGF-23), osteoprotegerin (OPG), osteocalcin (OC), procollagen type-1 N terminal propeptide (PINP), beta- crosslaps (beta CTx), tartrate resistant acid phosphatase (TRAP5b), bone alkaline phosphatase (BAP), 1,25(OH)D3, and 25(OH)D3 and α-klotho gene mutations were performed. RESULTS: In CPD patients, 1,25(OH)D3 and 25(OH)D3 deficiency rates were 96% and 94% respectively. iPTH (249 pg/mL vs 39 pg/mL) and FGF-23 (1089 RU/mL vs 153 RU/mL), OPG, OC, PINP, beta CTx, TRAP5b levels were significantly higher in patients. iPTH levels and whole-body BMD values were negatively correlated in patients. The rate of KGP was similar in all groups. CONCLUSION: In CPD patients, besides vitamin D deficiency, high levels of OPG, OC, PINP, beta CTx, TRAP5b were evident. Positive correlation between iPTH levels and BAP and PINP levels suggested a diagnostic value for those markers during the management of CKD MBD. On the other hand, high serum TRAP5b concentrations did not seem to be affected by neither calcitriol treatment nor the severity of hyperparathyroidism. iPTH and FGF-23 levels and whole-body BMD values showed a significant negative correlation. We were unable to show any correlation between KGP and any of the CKD-MBD parameters measured in this study.

Effect of platelet-rich plasma on wnt3 gene and klotho gene of adipose-derived stem cells of rabbit / 中华医学美学美容杂志

Objective To investigate the effect of platelet-rich plasma (PRP) on starting of wnt3 gene and klotho gene of adipose-derived stem cells (ADSCs) of rabbit.Methods Epididymal adipose tissue stem cells were obtained from New Zealand white rabbits,and the cells identified by morphology and inducing differentiation,and the cells were cultured to the fourth generation,PRP and PPP (platelet-poor plasma) were prepared by traditional centrifugal method from abdominal aortic of rabbit; ADSCs were cultured in culture medium containing PRP (experimental group),PPP (control group) and all medium (blank group) for each 5％ for 24h,48h and 72h.Cells of each group were dissociated and total RNA extracted.Effects of the starting of wnt3 gene and klotho gene were detected by RT-PCR.Results Primary ADSCs of rabbit grew in the way of long spindle swirly.The results of oil red O and alizarin red staining of the ADSCs were positive.Expression of wnt3 gene and klotho gene in the experimental group significantly increased from the results of RT-PCR (P＜0.05).Conclusions PRP can promote proliferation of the ADSCs of rabbit and increase the expression of wnt3 gene and klotho gene significantly.

Growth Hormone-Releaser Diet Attenuates Cognitive Dysfunction in Klotho Mutant Mice via Insulin-Like Growth Factor-1 Receptor Activation in a Genetic Aging Model.

BACKGROUND: It has been recognized that a defect in klotho gene expression accelerates the degeneration of multiple age-sensitive traits. Accumulating evidence indicates that aging is associated with declines in cognitive function and the activity of growth hormone (GH)/insulin-like growth factor-1 (IGF-1). METHODS: In this study, we examined whether a GH-releaser diet could be effective in protecting against cognitive impairment in klotho mutant mice. RESULTS: The GH-releaser diet significantly induced the expression of IGF-1 and IGF-1 receptors in the hippocampus of klotho mutant mice. Klotho mutant mice showed significant memory impairments as compared with wild-type mice. In addition, the klotho mutation significantly decreased the expression of cell survival/antiapoptotic factors, including phospho-Akt (p-Akt)/phospho-glycogen synthase kinase3ß (p-GSK3ß), phospho-extracellular signal-related kinase (p-ERK), and Bcl-2, but significantly increased those of cell death/proapoptotic factors, such as phospho-c-jun N-terminal kinase (p-JNK), Bax, and cleaved caspase-3 in the hippocampus. Treatment with GH-releaser diet significantly attenuated both decreases in the expression of cell survival/antiapoptotic factors and increases in the expression of cell death/proapoptotic factors in the hippocampus of klotho mutant mice. In addition, klotho mutation-induced oxidative stress was significantly attenuated by the GH-releaser diet. Consequently, a GH-releaser diet significantly improved memory function in the klotho mutant mice. GH-releaser diet-mediated actions were significantly reversed by JB-1, an IGF-1 receptor antagonist. CONCLUSION: The results suggest that a GH-releaser diet attenuates oxidative stress, proapoptotic changes and consequent dysfunction in klotho mutant mice by promoting IGF-1 expression and IGF-1 receptor activation.

Growth Hormone-Releaser Diet Attenuates Cognitive Dysfunction in Klotho Mutant Mice via Insulin-Like Growth Factor-1 Receptor Activation in a Genetic Aging Model

BACKGROUND: It has been recognized that a defect in klotho gene expression accelerates the degeneration of multiple age-sensitive traits. Accumulating evidence indicates that aging is associated with declines in cognitive function and the activity of growth hormone (GH)/insulin-like growth factor-1 (IGF-1). METHODS: In this study, we examined whether a GH-releaser diet could be effective in protecting against cognitive impairment in klotho mutant mice. RESULTS: The GH-releaser diet significantly induced the expression of IGF-1 and IGF-1 receptors in the hippocampus of klotho mutant mice. Klotho mutant mice showed significant memory impairments as compared with wild-type mice. In addition, the klotho mutation significantly decreased the expression of cell survival/antiapoptotic factors, including phospho-Akt (p-Akt)/phospho-glycogen synthase kinase3beta (p-GSK3beta), phospho-extracellular signal-related kinase (p-ERK), and Bcl-2, but significantly increased those of cell death/proapoptotic factors, such as phospho-c-jun N-terminal kinase (p-JNK), Bax, and cleaved caspase-3 in the hippocampus. Treatment with GH-releaser diet significantly attenuated both decreases in the expression of cell survival/antiapoptotic factors and increases in the expression of cell death/proapoptotic factors in the hippocampus of klotho mutant mice. In addition, klotho mutation-induced oxidative stress was significantly attenuated by the GH-releaser diet. Consequently, a GH-releaser diet significantly improved memory function in the klotho mutant mice. GH-releaser diet-mediated actions were significantly reversed by JB-1, an IGF-1 receptor antagonist. CONCLUSION: The results suggest that a GH-releaser diet attenuates oxidative stress, proapoptotic changes and consequent dysfunction in klotho mutant mice by promoting IGF-1 expression and IGF-1 receptor activation.

Effect of valsartan on ultrastructure in the brain tissue and expression of Klotho gene in spontaneously hypertensive rats / 中南大学学报(医学版)

Objective To observe the effect of valsartan on brian ultrastructure, Klotho gene and micro-inflammatory factor [intercellular adhesion molecule-1(ICAM-1) and vascular cell adhesion molecule-l(VCAM-1)] expression in spontaneously hypertensive rat models. Methods Ten male spontaneously hypertensive rats of 22 weeks age were selected and randomly divided into a hypertension group and a valsartan intervention group, while another 5 Wistar-kyoto rats were set as a normal contrast group. The brain ultrastructure of the 2 groups was observed by electron microscope. The expression of micro-inflammatory factor (ICAM-1 and VCAM-1)and Klotho gene was detected with RT-PCR, immunohistochemistry, and Western blot, respectively. Results The cerebral neuron damage of spontaneously hypertensive rats whose ultrastructure showed cell-pyknosis, chromatin margination and typical apoptotic body formation were alleviated after the intervention of valsartan. RT-PCR showed that the gene expression of Klotho increased while ICAM-1 and VCAM-1 decreased after valsartan intervention. Immunohistochemistry and Western blot also showed that the protein expression of Klotho increased, while ICAM-1 and VCAM-1 decreased after valsartan intervention. ConclusionValsartan can improve the brain ultrastructure of spontaneously hypertensive rats by increasing the expression of Klotho.