Effects And Mechanism Of Danggui Shaoyao San On Lipopolysaccharide-induced Pregnancy Hypertension In Rats

Aim: To study the intervention and antihypertensive mechanism of of Danggui Shaoyao San(DSS)on lipopolysaccharidein-induced pregnancy hypertension in rats,in order to provide experimental basis and basis for the clinical treatment of pregnancy induced hypertension by Danggui Shaoyao San.The therapeutic effect of DSS on lipopolysaccharidein-induced pregnancy hypertension in rats by means of average arterial pressure,24 h urine protein content,pathological morphology and function of kidney tissue in rats with pregnancy induced hypertension.On the basis of previous research,the mechanism of vasoconstrictor substance in pregnancy induced hypertension and the effect of Danggui Shaoyao San on vasoconstrictor substance were investigated from ET-1/ETB-e NOS/NO.Method:(1)A rat model of pregnancy induced hypertension was established by intraperitoneal injection of lipopolysaccharide(LPS).(2)The tail artery pressure in rats was measured by automatic noninvasive blood pressure measuring instrument.(3)24h urine in each group of rats was collected by metabolic cage,and the content of24 h urinary protein in rats was determined by BCA.(4)The levels of serum BUN,Cr were detected by the automatic biochemistry analyzer.(5)The content of serum NO was detected by the nitrate reductase method.(6)Enzyme-linked immunosorbent assay(ELISA)was used to detect serum endothelin 1(ET-1),tumor necrosis factor A(TNF-a)and interleukin 6(IL-6)levels in rats.(7)The renal tissue was stained with HE,and the pathological changes of the glomeruli were observed.(8)The relative expression of ETB and e NOS protein in placenta tissues was detected by Western Blot.Result:(1)Rat gestation 11 day intraperitoneal injection of LPS10ug·kg-1 for the first time,the next 5day to intraperitoneal injection of LPS40 g kg-1,once a day,reproducible and stable gestational hypertension model.(2)Compared with the model group,the average pulse pressure of rats in the different dose groups of DSS significantly decreased,and the 24 h urinary protein content decreased significantly(p<0.01).(3)The serum BUN,Cr levels were improved to varying degrees in DSS groups(p<0.05 or p<0.01).(4)The level of NO in the DSS group was higher than that of the model group(p<0.05 or p<0.01).(5)The plasma level of ET-1,TNF-a,IL-6significantly reduced in DSS groups(p<0.05 or p<0.01).(6)The glomerular pathological changes in the renal tissue of the rats were significantly improved than that of the model group.(7)The relative expression of ETB,e NOS protein were detected in placental tissue by Western Blot(p<0.05 or p<0.01).Conclusion:By intraperitoneal injection of LPS,stable pregnancy induced hypertension rats can be replicated.DSS has a therapeutic effect on LPS-induced pregnancy hypertension in rats: compared with the model group,it can significantly reduce the blood pressure,decrease the content of 24 h urine protein and the level of TNF-a and IL-6 in the serum,improve the renal function,improve the fetal growth restriction and abortion,delay the progression of the disease,and ensure the health of the mother fetus.The mechanism may be related to the increased expression of ETB receptor and e NOS protein in the placenta and the reduction of ET-1 concentration in the body and the increase of the concentration of NO in the body.