| Hypertension, along with high incidence of mortality and mobildity, is one of themost common cardiovascular diseases. Recently, it was reported that more than half of thepatients suffering from hypertension were accompanied by metabolic abnormalities, suchas hyperglycemia, hyperinsulinemia, hyperlipidemia, obesity and impaired glucosetolerance. The metablolic abnormalities may then aggravate hypertension induced vascularleision and promote vascular endothelial injury. It was believed that insulin resistance isthe basic factor of metablolic disorder, which makes a remarkable linkage betweenhypertension and insulin resistance. In the recent years, a lot of research documented thatinsulin resistance and hypertension make a reciprocal interaction and then increasevascular endothelial injury, leading to abnormal vascular structure and function andresulting in the damage of organs. So treatment of insulin resistance, along withanti-hypertension remedy, may remarkably protect vascular endothelial cells and providenew therapeutic methods for the treatment and prognosis of hypertension. Alpha-linolenic acid is a kind of polyunsaturated fatty acids extracted from plant.Compared with other polyunsaturated fatty acids, especially from sea food such as fish, ithas the remarkable advantage of low cost and easily acquisition. Recently, it was reportedthat alpha-linolenic acid dietary can prevent and treat cardiovascular diseases. It was alsoreported that alpha-linolenic acid can reduce blood lipid, lower blood pressure, reduceinflammation, inhibit platelet aggregation, inhibit thrombogenesis. However, thecardiovascular protective effects of alpha-linolenic acid is controversial. The related signaltransduction mechanism underling is still not clear.Our experiment was divided into three parts:Part1: the effects of alpha-linolenic acid on metabolism indexes of hypertensiveand insulin resistance rats induced by fructoseObjective: to clarify whether alpha-linolenic acid can inhibit the metabolic disorderinduced by hypertension and insulin resistance.Methods: we constrct the fructose induced insulin resistance and hypertension modelin accordance with the published literature.40male SD rats were fed normally for1weekand then were randomly divided into4groups：control group, fructose feeding group,alpha linolenic plus fructose feeding group and alpha linolenic feeding group.4weeks later,the metabolism indexes were detected. The blood pressure, serum triglyceride, serum totalcholesterol, serum glucose, insulin were detected by laboratory of Tangdu Hospital. Theserum Angiotensin II(AngII), nitric oxide(NO), malondialdehyde(MDA), superoxidedismutase(SOD), catalase(CAT) were detected by commercial kits.Results:(1) There was no significant difference in weight and serum total cholesterollever between four groups. Compared with control group, the systolic blood pressure,diastolic blood pressure, serum glucose, serum insulin, serum triglyceride and insulinresistance index were increased significantly in the fructose feeding group.Alpha-linolenic acid diet decreased the blood pressure, serum triglyceride, serum totalcholesterol, serum glucose, insulin and insulin resistance index significantly;(2) comparedwith control group, the serum MDA and Ang II were significantly increased while SOD,CAT, NO were significantly decreased in the fructose feeding group. Alpha-linolenic acid diet significantly decreased the level of serum MDA and AngII while significantlyincreased serum SOD, CAT, NO. There was no significant difference between controlgroup and alpha linolenic feeding group.Conclusion: the present study suggested that alpha linolenic acid can improvehypertension induced metabolic disorder, reduce insulin resistance and enhance sensitivityand antioxidant capacity of insulin.Part2.The protective effects of alpha-linolenic acid on rat vascular diastolicfunctionObjective: to detect whether alpha-linolenic acid improves vascular diastolicfunction in hypertension rats with insulin resistance and whether the IRS-1/AKT pathwayis involved.Methods: we constrct the fructose induced insulin resistance and hypertension modelin accordance with the published literature. After the SD rats were decapitated, thethoracic aorta were separated and cut into aortic ring for aortic dilation detection. Thedilation function of aortic ring exposed to different concentration of acetylcholine andinsulin were detected. The vasodilation morphology were observed with HE staining.IRS-1and Akt protein levels were detected by Western blot essay.Results: compared with control group, the endothelial dependent vasodilation wasdecreased in fructose feeding group. The alpha-linolenic acid treatment improved theendothelial dependent vasodilation, increased endothelial sensitivity to insulin, andpromote the insulin induced vasodilation. By HE staing detect, the four groups showeddifferent tissue pathological change. Compared with control group, the fructose feedinggroup showed significant medial thickening and proliferation of smooth muscle.Alpha-linolenic treatment reduced proliferation of smooth muscle proliferation and medialthickening. Compared with control group, the IRS-1phosphorylation was increased whileAkt phosphorylation was dereased in the fructose feeding group, alpha-linolenic aciddecreased IRS-1phosphorylation and increased Akt phosphorylation.Conclusion: the present study suggested that alpha linolenic acid show protective effect on endothelial dependent vasodilation and endothelial sensitivity to insulin. TheIRS-1/Akt signaling may be involved in this situation.Part3. Alpha-linolenic acid inhibites AngII induced endothelial cells apoptosisObjective: to detect whether alpha-linolenic acid inhibit angiotensin II inducedendothelial cell apoptosis and to explore the possible mechanism.Methods: the human umbilical vein endothelial cells(HUVECs) were cultured forexperiment. Endothelial cell apoptosis model were prepared by angiotensin II. Theconcentration of angiotensin II and alpha-linolenic acid were determined by detecting cellviability using MTT method. The HUVECs were randomly divided into four groups:control group, angII treated group, angII plus alpha-linolenic acid gropu and alphalinolenic acid group. The HUVECs were also exposed to LY294002. After cultured for24h, the MDA, SOD, CAT and NO were detected. Finally, tunel assay and flow cytometrydetection were used to detect cell apoptosis. Western blot was used to detect Aktphosphorylation，IRS-1phosphorylation and caspase-3expression level.Results: compared with angII group, alpha-linolenic acid decreased angII inducedMDA upregulation, enhanced SOD, CAT and NO expression, and significantly inhibitedangII induced cell apoptosis. Alpha-linolenic acid also increased the Akt phosphorylation,decreased IRS-1phosphorylation and decreased caspase-3level. The protective effects ofalpha-linolenic acid on cell apoptosis was decrease by LY294002treatement.Conclusion: the present study suggested that alpha linolenic acid show protectiveeffect on angII induced HUVECs apoptosis. The IRS-1/Akt/caspase3signaling may beinvolved in this situation. |
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