| Hemorrhagic shock is a common and severe syndrome in clinical practice. A large number of studies show that the low response state in the late stage of shock is an important factor in causing microcirculation disturbance and tissue perfusion. Research indicates that psothehorrhagic shock mesenteric lymph is one of the crucial factors causing organ damage. Blocking the shock of intestinal lymph reflux not only improve the body blood vessel reactivity and responsiveness of isolated vessels in highly severe shock rats, but also enhance the sensitivity of isolated vascular rings to gradient calciumion. The specific mechanism behind it is still under study., The renin angiotensin system?RAS? plays an essential role in hemorrhagic shock. The imbalance of ACE/ACE2 in RAS system is likely to deteriorate the multiple organ damage, the reason of PHSML drainage reduce the injury of renal and myocardium is the recovery of ACE/ACE2 Yet,it has not been reported whether the mechanism of vascular hyporeactivity mediated by hemorrhagic shock and PHSML have a relationship with the imbalance of ACE/ACE2. Therefore, the study show the effecton of mesenteric lymph duct ligation?MLD? on mesenteric microvascular reactivity and calcium sensitivitythe as well as the expression of ACE, ACE2 in superior mesenteric artery?SMA? and the contention of angiotensin II?Ang II? and Ang?1-7? in plasma in mice with hemorrhagic shock.Further the ACE2 gene knockout mice and the drugs which are related to ACE and ACE2 axis are used to discuss the role of the balance of ACE/ACE2 in vascular hyperactivity cause by PHSML,.First of all, the effect of MLV Ligation on the vascular reactivity of hemorrhagic shock in mice was observed. The 18 C57 male mice were randomly divided into three groups, i.e., Sham Group, Shock Group and Shock+Ligation Group. Three groups of mice were injected with pentobarbital sodium?70 mg/kg, 1%? and conducted abdominal surgery. Then the MLV of the mice was separated from SMA, followed by the thread running through the MLV, without ligation. Femoral operation was then administered, and the right femoral artery was stripped. Afterwards, the biological signal acquisition system was connected with MAP recorded and followed by an intubation on the left femoral artery. There was no other proceeding for the sham group after the surgery. At 30 minutes after the operation ended, the shock and shock+ligation groups bled to a state of shock. Rehydration therapy was conducted 1 hour after maintaining their shock state, and after that, MLV Ligation was conducted in the shock+ligation group, but not on the shock group. After 4 hours, Mesenteric secondary arteriole blood vessels of the mice were collected, which were then used for the preparation of in vitro micro vascular ring. The change of micro vessel to NE on the contraction reactivity and the sensibility of micro vessels to calcium were later tested by utilizing in vitro vascular tension system. The result shows that the MOD of ACE in SMA is significantly higher of mice in shock group than that in Sham Group?P<0.05?. Contrastively, the expression of ACE2 in the shock group is obviously lower than that in the sham group?P<0.05?. Besides, the MOD of ACE in SMA is significantly higher of mice in the shock+ligation group than that in the shock group?P<0.05?. Contrastively the expression of ACE2 in the shock+ligation group is obviously lower than that in the shock group?P<0.05?. Similarly, the content of Ang? in serum of mice in the shock group is significantly higher than that in the sham group?P<0.05?, while the content of Ang?1-7? is remarkably lower than its sham counterparts?P<0.05?. Furthermore, the content of Ang? in serum of mice in the shock+ligation group is significantly lower than that in the shock group?P<0.05?, while the content of Ang?1-7? is remarkably higher than that in the shock counterparts?P<0.05?. the reactivity of micro vessels to NE(1×10-6, 3×10-6, 1×10-5, 3×10-5 mol/L) of mice in the shock group is significantly lower that the sham counterparts?P<0.05?. However, the results show no significant difference in other concentration level?P>0.05?. In the meantime, the reactivity of micro vessels to NE(1×10-6, 3×10-6, 1×10-5, 3×10-5 mol/L) of mice in shock+ligation group is obviously lower that sham group counterparts?P<0.05?, yet remarkably higher than its in Shock Group(1×10-6, 3×10-6, 1×10-5, 3×10-5 mol/L)?P<0.05?. Besides, the reactivity of micro vessels to Ca2+(10-3,3×10-3,10-2,3×10-2,0.1,0.3 mol/L) of mice in Shock Group is significantly lower that sham group counterparts?P<0.05?. However, the results show no significant deviation in other concentration level?P>0.05?.The 18 C57 male mice were randomly divided into shock+enaprial group, shock+Ang?1-7? group and shock+losatain group. The shock models were produced same with the above methods. Rehydration was administered 1 hour after the shock with certain drugs added respectively. The samples were collected after 4 hours, among which, themesenteric secondary arteriole vasculars were used to test the vascular reactivity and its sensibility to Calcium.It is evident in the results that the reactivity of micro vessels to NE(3×10-7, 1×10-6, 3×10-6, 1×10-5, 3×10-5 mol/L) of mice in shock+enaprial group is significantly lower that shock group counterparts?P<0.05?. It is evident in the results that the reactivity of micro vessels to NE(1×10-6, 3×10-6, 1×10-5, 3×10-5 mol/L) of mice in shock+Ang?1-7? group is significantly lower that shock group counterparts?P<0.05?. the results show no significant between shock+location group and shock group?P>0.05?Besides, the reactivity of micro vessels to Ca2+(3×10-4,10-3,3×10-3,10-2 mol/L) of mice in Shock+Ang?1-7? ?Shock+Enaprial is significantly lower that Shock counterparts?P<0.05?. However, the results show no significant between Shock+Location group and shock group?P>0.05?.Finally, the roles of ACE/ACE2 play in Vascular Hyperactivity led by Intestinal lymph in mice following Hemorrhagic Shock. 6 ACE2 gene knock out mice and 9 C57 male mice were organized into three groups: shock+ligation+ACE2-KO ?shock+ligation+Ang??shock+ligation+A-779. The shock models were produced same with the above methods. Rehydration was administered 1 hour after the shock with certain drugs added respectively. After rehydration, mesenteric lymphatic vessels were ligated. The samples were collected after 4 hours, among which, the mesenteric secondary arteriole blood vessels were used to test the vessel reactivity and its sensibility to Calcium. The evidence indicates that the reactivity of micro vessels to NE(1×10-5, 3×10-5 mol/L) of mice in shock+ligation+ACE2-KO Group is significantly lower than shock+ligation counterparts?P<0.05?. the reactivity of micro vessels to NE(1×10-5, 3×10-5 mol/L) of mice in shock+ligation +Ang ? group is significantly lower than shock+ligation group counterparts?P<0.05?. However, the results show no significant statistical difference between shock+ligation+A-779 group and shock+ligation group?P>0.05?.The results show that the hyporeactivity of vascular and the decrease of calcium sensitivity have certain relations with hemorrhagic shock, after the mesenteric lymphatic circumfluence is blocked, the vascular reactivity and calcium sensitivity are enhanced. After hemorrhagic shock, the content of Ang? in serum and expression of ACE in SMA were increased significantly, while the content of Ang?1-7? and expression of ACE2 were restrained, this function can be limited by MLD.The expression of ACE-Ang?-AT1 axis in mice was inhibited and improvement was found in hyporeactivity of vitro vascular and the calcium sensitivity. Meanwhile, the results indicate that after Inhibition of ACE2-Ang?1-7?-Mas axis,the positive role that produced by MLC on improve vascular reactivity and calcium sensitivity were limited. ACE/ACE2 play a role in the reduce of vascular reactivity and calcium sensitivity in hemorrhagic shock, the function that PHSML mediate vascular hyporeactivity are related to the imbalance of ACE/ACE2;The other specific mechanism of action remains to be further studied. |
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