Mechanism Of "Huo-Xue-Xiao-Zhong" For Salvia Miltiorrhiza And Its Decoction And Their Effects On Lung Injurys Of Rats

Aquaporins are small integral membrane proteins that selectively transport water and some small solutes in mammals,plants and lower organisms.A family of 10 related molecular water channels,called aquaporins (AQPs),have been identifed in mamma1s.Each of them can increase the water permeability of plasma membrane and thus provide a route for rapid fluid movement.AQPs are expressed in many tissues such as the kidney,eye,and lung.Continued studies of the aquaporins are providing detailed tissue localization and the important physiological roles of aquaporins in urinary,respiratory,digestive and nervous systems.Based on the importance of aquaporins studies,in the field of clinic,aquaporins are related to many diseases,tumor,edema,disease of digestive system,nervous system disease,and so on.They are belong to"Shui-Zhong-Zheng"which is in the Traditional Chinese Medicine Diseases."Fei-Wei-Shui-Zhi-Shang-Yuan",it plays an important role in the body fluid metabolism."Xue-Bu-Li-Ze-Wei-Shui",blood stasis is related to edema.Aquaporin-1(AQP1) is the first aquaporin that was identified and revealed to be localized in the capillary membrane.AQP1is expressed in the alveolar capillary membrane in rats.A rat model of lipopolysaccharide (LPS)-induced acute lung injury (ALI) was used to evaluate whetherAQP1 is involved in lung inflammation and pulmonary edema (PE) formation. A number of pathologic conditions that affect the lung are characterized by disrupted fluid transport,including congestive heart failure,respireatory distress syndrome,and PE resulting from injury or infection.Immunohistochemical analysis showed a significant decrease in the expression of AQP1 in injured lungs at 4-48h after LPS instillation.AQP1 protein was resumed partly at 24h after LPS instillation administration.The decreased expressions of AQP1 in injured lungs suggest that it may play a role in abnormal fluid transportion.Chinese materia medica promoting blood flow may be related to the relationship of blood stasis and body fluid regulation. Chinese materia medica of"Huo-Xue-Hua-Yu"method and their complex decotions can regulate the expression of AQPs.Salvia miltiorrhiza (SM) is a common Chinese materia medica of"Huo-Xue-Hua-Yu"method.It can regulate blood fluid,decrease blood viscosity,improve microcirculation(MC) as results.But there is no report about whether SM can regulate the AQP1 which is in the microvascular endothelial cell (MVEC).In the experiment,the model of ALI and diabetic nephropathy (DN) were edtablished in rats.The purpose was to determine whether AQP1 is expressed in the alveolar capillary membrane in rats mode1.Furthermore,we investigated the alteration of AQP1 in ALI and DN rats induced by LPS and streptozocin (STZ).The effect of SM and its complex prescription on AQP1 in acute PE and chronic lung injury (CLI) was also observed in order to supply proofs to clinical evaluation of Chinese materia medica promoting blood flow.Exprimentâ… Effects of Salvia miltiorrhiza on lungs in rats model of LPS-induced ALI and on AQP1Objective:To investigate the effect of salvia miltiorrhiza(SM) on aquaporin-1(AQP1) expression in rats with acute lung injury(ALI) induced by lipopolysaccharide(LPS). Method:48 SD rats were randomly divided into normal group, SMIprevention group, ALI 7-day group, SMI 7-day treatment group,ALI 8-hour group, and SMI 8 -hour treatment group,8 rats per group.At 8 hours and 7 days after treatment,lung wet-to-dry(W/D) weight ratio,lung pathology,electronmicroscope,AQP1immunohistochemistry(IH),and AQP1 Western blot(WB)were performed.The situation of hemorheology and the PaO2,Endothelin-1(ET-1) levels in the serum were also detected. Results:Compared with the normal group,the figures of PaO2 significantly decreased in model groups.(P<0.05);respiratory rate (RR) significantly increased (P<0.05);treatment groups and SMI prevention group significantly increased compared with the model groups(P<0.05).Compared with the normal group, the figures of ET-1 significantly increased in model groups;treatment groups and SMI prevention group significantly decreased compared with the model groups (P<0.05).The model group rats all appeared ALI symptom. Compared with the ALI 7- day group, the degree of lung edema statement alleviated in SMI 7-day treatment group.But the expression of AQP1 was not significant between the two groups(P<0.05).Compared with the ALI 8- hour group,the degree of lung edema statement alleviated in SMI 8-hour treatment group and SMI prevention group.The expression of AQP1 was significantly expression in the group of SMI prevention group (P<0.01).Exprimentâ…¡The Alternation Of The Expression Of AQP1 With SM Complex Decoction (Ze-Huang apozeme) In Lung Tissues In DNObjective:To observe the expression and activities of AQP1 in pulmonary tissues in diabetic rats. Method:40 SD rats were randomly divided into normal group,model group,control group,observe group,10 rats per group.Diabetic model rats were induced by intraperitoneally injected streptozotozin (STZ).After 4 months,we detected fasting blood glucose(FBG),serum creatinine (SCR),blood urea nitrogen(BUN) and observed the pathologic changes in lungs,tested AQP1 by IH method.Determined the expression of AQP1 using IH analysis. Results:DN rats appeared"polyphagia,polydipsia and polyuria"symptoms,abdominal distension in later period. The rats in control and observe groups appeared well.Compared with the normal group,FBG,Scr,Bun all increased in model group(P<0.05),the rate of RR also significantly increased(P<0.05);control and observe groups significantly decreased(P<0.05).We observed thickened pulmonary capillary basal lamina and increasing number of fibres in DN rats. Compared with the normal group,the expression of AQP1 decreased in the model group.Compared with the model and control group,the expression of AQP1 increased in the observe group. Conclusion:1 PE is the main syptom in ALI induced by LPS. SM may alleviate the degree of the lung edema by regulating the expression of AQP1,improve the lung fluid conveying and the situation of hemorheology.The mechanisms that"Huo-Xue-Xiao-Zhong"of SM may be related to regulating AQP1.It may be the essence of"Huo-Xue-Xiao-Zhong"method.2 The AQP1 was decreased in diabetic lung which is in the imbalance of microcirculation.The AQP1 plays an important role in diabetic lung(lung edema).The SM complex decoction can regulate the activities of AQP1 to improve the imbalance of the water metabolism of lung tissue. It reavels that the effects of SM and its complex prescriptions regulate the expression of AQP1 may be related to the"Huo-Xue-Hua-Yu/Huo-Xue-Xiao-Zhong".3 The particular distribution of AQP1 on MVEC in lung and the regulation of SM on the expression of AQP1 suggests a new pharmacological effect of SM. It is the modern medicine explanation of"Tong-Tiao-Shui-Dao".