Expression And Clinical Significance Of Klotho Protein In Placentas From Women With HDCP

Hypertensive disorders complicg patinregnancy (HDCP) is a specific disease during pregnancy,is characterized by hypertension after 20 gestational weeks,proteinuria ,edema,and accompanied by multiple organ damage, The disease seriously affect maternal and child health, is one of the main reasons of leading to maternal and perinatal disease and mortality .The theories about the causes and pathogenesis of HDCP are not fully clarified ,this is the important research subject of present obstetrics. Research proves, the happening of HDCP is related with vascular endothelial cell injury, vascular endothelial relaxing factor nitric oxide (NO) play a role in adjusting vascellum for maintaining normal pregnancy, and closely related to the pathogenesis of HDCP.Klotho gene is a important anti-aging gene that we knew, it was discovered by Kuro-o etc when they researched spontaneously hypertensive in 1997. This gene is located on the human No.13 chromosome. Kidneys, placenta, small intestine and prostate are expressed,its expression product is Klotho protein,which includes two types in the body, the secretory type and binding type. Klotho protein is related to various pathophysiological change of cardiovascular system, its action mechanism mainly through adjusting endogenous NO release ways and thereby protect vascular endothelial. Animal models have confirmed that Klotho protein can increase the synthesis of endogenous NO,the lack of Klotho protein directly or indirectly cause NO synthesis reduction, but the mechanism is unclear. At present more authoritative hypothesis believe that, Klotho protein as a kind of enzyme make precursor substances become bioactive substances, the loss of Klotho gene caused the active of NO synthase decrease, increase NO product. In mice, Klotho gene mutations caused cardiovascular system damage badly, the sensitivity of aortic and small artery blood vessels to acetylcholine decline ,and this kind of endothelial injury can be restored to near-normal by Klotho protein itself or other Klotho protein related circulating factors, through Klotho gene transduction in adenovirus can improve endothelial injury, increase NO product, reduce the heightened blood pressure; Klotho genes involved in adjusting angiogenesis, promoting capillary generation, this effect is more apparent especially in ischemic tissues, its action mechanism may be adjustment endothelial function through NO pathway; Klotho protein can strengthen the activity angiotensin converting enzyme, play a role in moderate blood pressure, balance water and salt and maintain homeostasis, this has dose-response with Klotho protein. It was speculated that Klotho protein can maintain the dynamic balance of RAS system and endogenous NO,and regulate vascular tone because it can increase the synthesis of endogenous NO; Excessive Klotho gene expression can protect kidney damage by AngⅡ, AngⅡis an important factor in the process renal damage development of hypertensive, directly cause renal fibrosis, eventually cause renal failure, the long time perfusion of AngⅡcan down-regulated Klotho mRNA and the expression of Klotho protein in kidney, the transfection of adenovirus carrier with Klotho genes by vein can reduce albuminuria, improve renal function, and significantly reduce damage of renal tubule interstitium. There haven't the research with Klotho protein and Hypertensive disorders complicg patinregnancy (HDCP) at home and abroad. This study discusses the function and clinical significance Klotho protein in HDCP pathogenesis through detecting the expression condition of Klotho protein in placentas of normal pregnant women and HDCP patients.The experiment collects HDCP patients 40 cases(10 gestational hypertension patients,20 preeclampsia patients,10 eclampsia patients)and normal pregnant women(20 cases)from the Second Hospital of Jilin University,and adopts immunohistochemistry to detect the expression condition of Klotho protein in placenta tissues.Experimental data apply statistical software SPSS17.0 for statistical analysis,comparison among the groups adopts One-way ANOVA,and correlation analysis adopts Pearson correlation test.Experimental results show that: Klotho protein has brown positive staining particle expression in placenta tissue syncytiotrophoblast(STBM) and the cell membrane and cytoplasm of STBM, corresponding nuclei are blue.The average grey level of Klotho protein in normal pregnant group are: 104.76±2.38, e average absorbance values in the HDCP group are 154,22±2.20 , 124.26±2.44 and 194.92±1.76。The expression of Klotho protein in HDCP group is significantly lower than that in the normal pregnancy group. The bigger the grey level is ,the positive rate is smaller. And its expression strength as follows :gestational hypertension group﹥preeclampsia group﹥eclampsia group, the difference was statistically significant (P < 0.001), The expressions of them in each group show negative correlation.In summary,the following conclusions can be obtained: Klotho protein show high level expression in placenta tissues of normal pregnant women and may be involved in adjusting the synthesis of NO in normal pregnancy ;the Klotho protein show low level expression in placenta tissues of HDCP patients and may be related with the pathogenesis of HDCP;Its expression strength as follows :gestational hypertension group﹥preeclampsia group﹥eclampsia group, the difference was statistically significant (P < 0.001), indicating that it may have negative correlation with the severity of disease. In-depth understanding of expression and significance of Klotho protein in the placenta tissues has important value for elucidating endothelium injury mechanisms,and provides a new way of thinking for diagnosis and treatment of HDCP at the same time.