| Ginsenoside Rg3(Rg3)is a rare saponin produced by ginseng in the process of high temperature processing,and has excellent antitumor activity.At present,domestic pharmaceutical companies have industrialized Rg3 production and developed a new class of Chinese medicines that are complementary to anti-tumor drugs.They have been widely used in clinical practice and have achieved good results.In addition,several studies have shown that Rg3 also has a good cardiovascular protective effect,including anti-inflammation,anti-oxidative stress,anti-fibrosis and regulating the activity of renin-angiotensin system(RAS).Hypertension often causes kidney damage,and kidney disease is one of the important reasons for the development of hypertension.Hypertension and kidney disease are mutually causal,often cause a vicious circle,and eventually develop into severe hypertension and chronic end-stage renal disease,which is one of the major threats to human health.RAS plays a key role in the progression of kidney disease and hypertension to each other.Angiotensin-converting enzyme inhibitors(ACEI)and angiotensin type 1 receptor antagonists(ARB)are first-line drugs for clinical prevention,treatment of renal hypertension and hypertensive nephropathy.In our previous study,our group found that Rg3 can inhibit myocardial fibrosis and slow down by down-regulating angiotensin II(Ang II)and inflammation levels in myocardial tissue in a spontaneously hypertensive rat(SHR)model.Blood pressureinduced ventricular remodeling in rats improves their cardiac function.Hypertension can also cause kidney damage in SHR.As mentioned earlier,RAS dysfunction is an important mechanism of SHR injury.In view of the role of Rg3 in the prevention of RAS,inhibition of inflammation and fibrosis in the prevention of SHR heart injury,we conducted a study on the prevention of SHR renal injury by Rg3.The results showed that although Rg3 could not significantly reduce the blood pressure of SHR,Rg3 could effectively alleviate renal injury and pathological changes of SHR by reducing Ang II in kidney tissue and inhibiting Ang II-mediated inflammation,oxidative stress and fibrosis.The mechanism may be that Rg3 up-regulates the expression of angiotensin-converting enzyme 2(ACE2),which is capable of degrading Ang II in kidney tissue.To further confirm the remission and mechanism of Rg3 on Ang II-induced hypertensive renal injury,we used microcapsule osmotic pump to subcutaneously release Ang II into mice,causing kidney damage in mice and treatment with Rg3.Observe its effect and analyze its mechanism of action.The results showed that Rg3 also had a remission effect on mouse kidney injury caused by exogenous Ang II.The mechanism was still up-regulated by up-regulation of ACE2 expression in kidney tissue,increased Ang II degradation,and inhibition of Ang II-mediated Inflammation,oxidative stress and fibrosis.To demonstrate that ACE2 up-regulation is a key mechanism by which Rg3 plays a role in renal protection,we constructed ACE2 knockout mice(KO).Continued use of microcapsule osmotic pump to subcutaneously release Ang II in mice to induce kidney damage in mice,compared with the difference in renal protection of Rg3 in wild-type(WT)mice and KO mice.The results showed that Rg3 could not increase the degradation of Ang II by up-regulating the expression of ACE2 in the kidney tissue of KO mice,and had no obvious inhibitory effect on Ang II-mediated inflammation,oxidative stress and fibrosis.Therefore,there was no significant alleviation of Rg3 in renal injury of KO mice caused by exogenous Ang II.According to reports in the literature,spontaneous hyperglycemic mice(db/db)in the early stage of elevated blood glucose,the expression of ACE2 in the kidney tissue will be compensated up,play a certain role in kidney protection,slow the progression of diabetic nephropathy.However,as the mice age,the compensatory up-regulation of this ACE2 will gradually fail,and the kidney damage of the mice will enter the decompensated period and develop into diabetic nephropathy.In view of the fact that Rg3 also up-regulated ACE2 in kidney tissue during the prevention of hypertensive nephropathy,we used Rg3 to treat db/db mice,observed the renal protective effect of Rg3,and analyzed the effect of Rg3 on the expression of ACE2 in kidney tissue.The results showed that Rg3 could not significantly reduce the blood glucose of db/db mice,but it could prolong the compensatory up-regulation of ACE2 in the kidney tissue of db/db mice,thereby reducing the level of Ang II in kidney tissues and inhibiting Ang II mediated.Inflammation,oxidative stress and fibrosis play a role in kidney protection,further slowing the progression of diabetic nephropathy.In summary,Rg3 can slow the progression of hypertensive nephropathy in SHR and diabetic nephropathy in db/db mice by up-regulating ACE2 in kidney tissue.In addition to its good anti-tumor effect,Rg3 is widely used as a drug for adjuvant treatment of tumors,and has potential as a drug for adjuvant treatment of hypertension,diabetes,and prevention of renal complications.In addition,recent studies have shown that up-regulation of ACE2 in the tumor microenvironment may help inhibit tumor invasion and metastasis.Therefore,up-regulation of ACE2 expression in tissues may be one of the common mechanisms by which Rg3 exerts anti-tumor,cardiovascular and renal protective effects,which needs to be verified by more experiments. |
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