| Background and Objectives:hypertensive disorders comlicating pregnancy is a disease unique to pregnancy, is characterized by hypertension, proteinuria and edema after 20 weeks of pregnancy, Accompanied by systemic multiple organ damage. The disease severely affect health of infants and woman, hypertensive disorders comlicating pregnancy may play a major role on the diease's occurrence and development. The incidence rate is 9.4% in our country, and foreign reports 7%-12%.The occurrence of diseases originate pathophysiological changes in placental, hypertension Status cause vascular endothelial cell injury, that cause severe ischemia of the brain, heart, lung, liver, kidney and other important organs, kidney damage is characteristic of its early stage,but the mechanism of kidney damage rarely reported at home and abroad.Characteristic of renal damage is mainly manifested as proliferation of glomerular capillary wall and basement membrane and occurrence proteinuria.Molecular mechanmis of renal damage is unknown in the word, recent studies found that the imbalances of extracellular matrix (ECM) synthesis and degradation are important reasons of primary renal disease or secondary nephropathy for occurrence and development.Matrix metalloproteinase 9 (MMP-9)and heparanase (HPA)is the ECM degradation enzymes,that's expression is import reason in kidney damage with hypertensive disorders comlicating pregnancy. There is no effects of drugs clinical, but has the experience with the use of heparin in the treatment, heparin easily lead to bleeding, Low molecular weight heparin (LMWH) is extracted from the unfractionated heparin with a bleeding less side effects and high bioavailability, that's biological effect is mainly anticoagulant, expand blood vessels, lower blood pressure, reduce cell proliferation of glomerular basement membrane. This study was prepared animal model of hypertensive disorders comlicating pregnancy and treat with LMWH intervention, observing the expression of MMP-9and HPA in rats kidney tissue with hypertensive disorders comlicating pregnancy and the intervention effect of low molecular weight heparin, to discuss the role of MMP-9 and HPA in kidney damage with hypertensive disorders comlicating pregnancy. Materials and Methods:(1)TO prepare and group animal model of hypertensive disorders comlicating pregnancy:Take the normal Wistar female rats 45,2:1 according to male and female co-CAGE, to take the female vaginal secretion smears every moring, Found that sperm counts as the first Id Pregnancy. The pregnant rats were randomly divided into 3 groups, normal pregnancy group, hypertensive disorders comlicating pregnancy group and the LMWH intervention group of 15 rats, The pregnant rats of hypertensive disorders comlicating pregnancy group subcutaneous N-nitroso-L-arginine methyl ester (L-NAME) 250 mg/kg on the 14th day of pregnancy, The pregnant rats of LMWH intervention group subcutaneous injection of L-NAME250 mg/kg (am) andLMWH 600IU/kg (pm) on the 14th day of pregnancy, The normal pregnancy group injected the same amount of saline,once a day. Another take 15 healthy pregnant and unmated female age as normal control group. Four groups measure rat tail artery blood pressure daily and collect 24-hour urine to determine urinary protein the next day on the 12th day of pregnancy. (2)Specimen collection:taken some Kidneys fix 10% of formaldehyde solution immersion in the pentobarbital sodium (50mg/kg) anesthesia on the 21th day of pregnancy to HE staining and immunohistochemical staining. Collection 24-hour urine to determine urinary protein use of sulfur salicylic acid-sodium sulfate turbidimetry, bovine serum albumin as a standard protein. (3)Immunohistochemistry:The expression of Kidney tissue MMP-9 and HPA determined by immunohistochemical staining, Steps according to kit instructions. (4) Statistical analysis:using SPSS 13.0 statistical software process data that expressed as mean±standard deviation (x±s), comparison of the mean between the two groups use t test, correlation analysis use spearman rank correlation, Significance level of a= 0.05.Results:1.Laboratory test results:mean arterial pressure and urine protein of the rats of hypertensive disorders comlicating pregnancy group began to increase on the 14th day of pregnancy, in the end of delivery significantly increased than the other two groups. LMWH intervention group mean arterial pressure and urine protein,compared with hypertensive disorders in pregnancy group was significantly lower, but not yet reached the level of normal pregnancy.2. Histopathological changes of kidney:The HE staining of kidney tissue in hypertensive disorders comlicating pregnancy group showed some glomerular mesangial cells and some basement membrane cell proliferation, mesangial matrix increasion, glomerular arterial wall hyaline degeneration. LMWH intervention group mesangial cells and basement membrane cell proliferation to reduce.3. The expression of MMP-9 and HPA in kidney tissue: There is no expression of MMP-9 and HPA in glomeruli, only a slight expression in renal tubular in the normal control group; The expression of MMP-9 and HPA in the glomerular in the normal pregnancy group increased than the control group; The expression of MMP-9 and HPA in the glomerular in hypertensive disorders comlicating pregnancy group are significantly increased compared with normal pregnancy; The expression of MMP-9 and HPA in the glomerular in LMWH intervention group compared with in hypertensive disorders in pregnancy group are significantly weakened, but have not yet reached the level of normal pregnancy.4. The expression of MMP-9 and HPA in the glomerular is positive correlation.Conclusions:1. The expression of MMP-9 and HPA in rats kidney tissue in hypertensive disorders comlicating pregnancy group was significantly higher than normal pregnant group and the normal control group.The increased expression of MMP-9 and HPA in kidney tissue may be one of the mechanisms of renal damage in hypertensive disorders in pregnancy.2. The expression of MMP-9 and HPA in the kidney tissues are positively correlation, HPA may promote the expression of MMP-9, And may be shared with the MMP-9 play a role in promoting renal damage in hypertensive disorders comlicating pregnancy.3. The expression of MMP-9 and HPA in the rat kidney tissue in LMWH intervention group reduced than the hypertensive disorders comlicating pregnancy group. LMWH has a protective effect in the renal damage in hypertensive disorders comlicating pregnancy.
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