The Relationship Between Aortic Remodeling And Autophagy In Spontaneously Hypertensive Rats—An Intervention Study Of Berberine

Objective: To explore the relationship between aortic remodeling and autophagy in spontaneously hypertensive rats(SHR), and the potential role of berberine in regulating this relationship.Methods: Forty 11-week-old healthy male spontaneous hypertension rats were randomly divided into 5 groups:lower-dose berberine group(30mg/kg/d,BL),medium-dose berberine group(90mg/kg/d, BM), high-dose berberine group(270mg/kg/d,BH),Antihypertensive group(telmisartan,8mg/kg/d,T),hypertension group(S), 11-week-old healthy male Wistar-Kyoto rats as the control group(W,n=8).After 1 week feeded,all rats were intervened for 24 weeks.(1)Systolic blood pressure(SBP) was monitored by the standard tail-cuff method every 2 weeks;(2) After the experiment,the aortic ring function(systolic function 、endothelium-dependent vasodilation and endothelium-independent vasodilation) were detected;(3) Collagen area of aorta tissue was measured by EVG staining, while media thickness(MT), lumen diameter(LD) and medial area(MA) were evaluated with HE staining;(4) Microtubule-associated protein 1 light chain 3(LC3) expressions on aorta tissue were measured with immunohistochemistry;(5) Protein expressions of inducible NOS(i NOS)、phosphatase and tensin homolog deleted on chromosome ten(PTEN)、Beclin1、total Akt(t-Akt)、phosphorylation of Akt(p-Akt)、total m TOR(t-m TOR)、phosphorylation of m TOR(p-m TOR) on aorta tissue were measured with Western blot.Results: 1.The blood pressure of berberine treatment groups had no significant decline(p > 0.05); The treatment which SHR feed telmisartan treatment could decrease blood pressure(p<0.01). 2.BM、BH and T group improve systolic function and endothelium-dependent vasodilation of aorta(p<0.05). Berberine treatment groups couldnot improve endothelium-independent vasodilation of aorta(p >0.05).3.MT,LD,MA and collagen area of BH and T group were less than S(p<0.01), and no change happened to BL and BM group(p>0.05).4.S group had a higher expression of LC3 and Beclin1 when compared to W group(p<0.05). BM、BH and T group had a higher expression of PTEN 、LC3、Beclin1 but a lower expression of p-Akt/ t-Akt and p-m TOR /t-m TOR when compared to S group(p<0.05).Conclusions: Autophagy is enhanced in SHR when aortic remodeling. The present study showed that berberine is effective in promoting autophagy, and subsequently improving systolic function and endothelium-dependent vasodilation of aorta and reduce aortic remodeling. The potential underlying mechanism is augmentation of autophagy through inhibition of PI3K/Akt signalling pathways.