| Objective:1. To elucidate the effect of various biochemical indicators, including somecoagulating and fibrinolytic factors on SD rats fed by normal diet or sucrose andfat rich diet and supplied simultaneously of α-linolenic aicd(ALA) and deep-seafish oil(FO) for long-term. Especially, to investigate the preventive effect of n-3PUFA on the risk of type2diabetes mellitus(T2DM) and concurrentmicroangiopathy on SD rats fed by sucrose and fat rich diet, and provide theevidence of fundamental research for rationality of n-3PUFA supply on peoplehaving different diet structure.2. To elucidate the effect of various biochemical indicators, including somecoagulating and fibrinolytic factors on T2DM SD rats, and provide the evidenceof fundamental research for rationality of n-3PUFA supply on T2DM people.3. To investigate the effect of n-3PUFA on serum free fatty acids(FFA) ofSD rats and the metabolic reason of n-3PUFA’s effect. At the same time, toinvestigate the relativity between the content change of serum FFA and everybiochemical indicator, and the effect of FFA on IR, coagulation and fibrinolysissystem of SD rats. Methods:1. In the first experiment, the rats fed by normal diet and sucrose and fatrich diet were used to imitate the people with the same eating habits respectively.140SD rats were divided in14groups randomly and there were half of maleand female rats in each group with total10. The groups were divided asfollowing: blank control group(BC group, fed by normal diet), sucrose and fatrich diet group(SF group, fed by sucrose and fat rich diet), ALA groups and FOgroups fed by normal diet, ALA groups and FO groups fed by sucrose and fatrich diet. According to the state of division, the ALA groups and the FO groupswere administered respectively with ALA and FO on three different does of600,300,150mg/kg by gavage for successive8weeks. The rats were fasted but notremoved water for12hours after the last administration, and then anaesthetizedwith10%chloral hydrate by intraperitoneal injection. The blood from theabdominal aorta was used to detect the liver function, renal function, fastingblood-glucose, fasting insulin, four items on blood lipid and some coagulatingand fibrinolytic factors etc.2. In the second experiment, sucrose and fat rich diet feeding uniting withstreptozotocin(STZ) intraperitoneal injection was used to prepare the model ofT2DM SD rats. When the fasting blood-glucose level was stable, the T2DM ratswith fasting blood-glucose level from7.8to15mmol/L were divided into8groups randomly and there were half of male and female rats in each group withtotal10. The groups were divided as following: T2DM control group(T2DMgroup), rosiglitazone control group(ROS group), ALA and FO three differentdose groups. Another10rats without being made T2DM model were regardedas blank control group(BC group) fed by normal diet; the other groups were fedby sucrose and fat rich diet. According to the state of division, the ALA and FO groups were administered respectively with ALA and FO on three different doesof600,300,150mg/kg by gavage for successive4weeks. The rats were fastedbut not removed water for12hours after the last administration, and thenanaesthetized with10%chloral hydrate by intraperitoneal injection. The bloodfrom the abdominal aorta was used to detect the liver function, renal function,fasting blood-glucose, fasting insulin, four items on blood lipid and somecoagulating and fibrinolytic factors etc.3. The third experiment was carried out the content determination byGC-MS of FFA on the serum samples from the first and second experiment.And then the correlation analysis was made between the results of FFA contentdetermination and every biochemical indicator.Results:1. There wasn’t any significant effect of ALA on SD rats fed by differentdiet when they were adminstated with ALA by gavage for8weeks. FO coulddecrease the level of AST and TC significantly in the rats fed by sucrose and fatrich diet(p<0.01and p<0.05), and at the same time enhance the rise trend ofhs-CRP(p<0.01). FO could inhibit the secretion of pancreatic β cells andincrease the level of fasting blood-glucose in rats fed by different diet(p<0.05).2. There wasn’t any significant effect of ALA on coagulation andfibrinolysis system of SD rats fed by different diet. There wasn’t any significanteffect of FO on coagulation and fibrinolysis system of SD rats fed by normaldiet, but the synchronous ingestion of FO and the sucrose and fat rich diet wouldcause the APTT decrease significantly (p<0.05).3. n-3PUFA could decrease the level of AST significantly in the T2DM SDrats and FO was more effective than ALA on it（p<0.05）. Besides, there wasn’tany other significant effect of n-3PUFA on T2DM SD rats. 4. There wasn’t any significant effect of ALA, including the abnormalincrease of EPA and DHA, on serum FFA in SD rats fed by different diet. Thesucrose and fat rich diet feeding could make the content of C18:1risesignificantly(p<0.01). The intragastric administration of FO could make thecontent of C22:6in rats fed by different diet rise significantly on certaindose-effect relationship(p<0.05).5. Compared with the BC group, the content of serum FFA level in the ratsof T2DM group increased significantly(p<0.01). The supply of n-3PUFA had noany significant effect on this increase.6. The content of C18:1in rats fed by different diet was positivelycorrelated with hs-CRP, TC, LDL, FIB and TAT respectively(p<0.01); thecontent of C22:6was positively correlated with FBG and hs-CRP respectively(p＜0.01and p＜0.05), and negatively correlated with FINS and HOMA-ISrespectively(p<0.01).7. The content of serum FFA in T2DM SD rats including C16:0, C18:0,C18:1, C18:2, C20:4and C22:6, were all positively correlated with ALT, Ure,FBG, HOMA-IR, hs-CRP, TC, TG, HDL-C, LDL-C, FIB, TAT, t-AP and PAI-1respectively(p<0.01or p<0.05), at the same time, were all negatively correlatedwith HOMA-IS and APTT respectively(p<0.01).Conclusions1. ALA had no any significant effect on many biochemical indicators ofnormal SD rats fed by different diet or T2DM SD rats.2. FO could decrease the level of AST and TC significantly in the normalrats fed by sucrose and fat rich diet, but at the same time, the synchronousingestion of FO and the sucrose and fat rich diet would cause the increase ofinflammation and hyperfunction of coagulation in normal rats. Besides, the long-term and excessive ingestion of FO could increase the content of C22:6inthe blood, lead to injury of normal pancreatic β cells, damage of insulinsecretion ability, increase the risk to diabetes of normal SD rats.3. Except for inhibiting the rise of AST, FO had no any other adjunctivetherapy function on T2DM SD rats.4. The negative effect was much more than positive effect of the long-termand excessive ingestion of n-3PUFA on normal SD rats, so whether the normalpeople should make the extra supply of n-3PUFA still needing more proof fromclinical research to confirm. n-3PUFA had little adjunctive therapy function onT2DM SD rats, so whether the T2DM patients should make the extra supply ofn-3PUFA also needing more proof from clinical research to confirm. |
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