| Part I Study on the effects of metabolism on diabetic erectile dysfunctionObjective: To observe the effects of metabolic control on erectile function in male patients with diabetes erectile dysfunction.METHODS: Newly diagnosed male type 2 diabetes mellitus in our hospital from 2015 to 2018(diagnosed by the American Diabetes Association Diabetes Diagnostic and Classification Standards by standard OGTT test)combined with Erectile Dysfunction(ED)(IIEF-5<21)Divided into 80 patients(excluding cardiogenic ED),based on dietary exercise therapy,intensive glycemic control,lipid-lowering and other metabolic therapy for 6 months to achieve control objectives: FBG ≤ 6.0 mmol / L,PBG ≤8.0 mmol/L,Hb A1c≤6.5%,CHO <4.6mmol/L,TG<1.7mmol/L,and the ED was evaluated by the International Erectile Function Index(Questionnaire)(IIEF-5)before and after the study.RESULTS: Ten patients experienced significant improvement in symptoms after treatment,and the IIEF-5 questionnaire scored >21.The remaining patients did not significantly improve their symptoms after treatment.The scores of the IIEF-5 questionnaire before and after treatment changed from(13±1.6)to(16±0.8)(P>0.05).Conclusion: The strict control of blood glucose in newly diagnosed male patients with diabetic erectile dysfunction does not significantly improve diabetic erectile dysfunction.Part II Effect of Jinlida on high glucose-induced rat corpus cavernosum smooth muscle cell functionOBJECTIVE: To investigate the effect and mechanism of Jinlida granule on phenotype transformation and apoptosis of rat corpus cavernosum smooth muscle cells(CCSMCs).Methods: 1.Primary SD rats were subcultured with CCSMCs.All cells were incubated with 5.5mmol/L glucose for 24 h and then divided into7 groups according to the changed medium: 1 normal sugar group(NG):physiological concentration of glucose 5.5 mmol/L;2 high glucose group(HG): glucose 25 mmol/L;3 hypertonic group(HC): mannitol25 mmol/L(this group of osmotic pressure is the same as high glucose group,used to identify high glucose induced Whether the damage originated from high glucose or high osmotic pressure);4 high glucose + PD98059 group(HG + PD),glucose 25 mmol / L + 50 μmol/ L PD98059,PD98059 added HG 30 min in advance;5 high sugar + low concentration Jinlida group(HG+LJLD): glucose 25 mmol/L+jinli up to 50 mg/L,glucose treatment after adding 25 mmol/L for 1 hour;6 high glucose+medium concentration Jinlida group(HG+MJLD)):glucose 25 mmol / L + Jin Lida 150 mg / L,dosing order is the same as before;7 high sugar + high concentration Jin Lida group(HG +HJLD): glucose 25 mmol / L + Jinli up to 300 mg / L,dosing The order is the same as before.After treatment,the cells were observed at0,24,and 48 h,and the cells were observed at high magnification.The cells were collected at 48 h.Western blot was used to detect alpha smooth muscle actin(α-SMA)and alkaline tone.Expression of calponin1 and osteopontin(OPN);expression levels of signaling pathway proteins ERK1/2,p-ERK1/2,caspase-3 and bcl-2;flow cytometry Apoptosis.result: 1.CCSMCs grow and form part of a single layer,the arrangement begins to show directionality,multi-parallel arrangement,when the cell density is high,it is arranged in a bundle or vortex,and some areas are up and down,showing typical "peak-valley"-like smooth muscle cell characteristics(Figure 1-1).In subculture,CCSMCs began to form long fusiform and star-shaped,with the prolongation of culture time and the increase of cell density.When cells were fused,some regions overlapped in multiple layers.In the NG group,with the prolongation of time,the growth of CCSMs was good and the survival rate was high;the cells were mostly bundled or spiral,arranged more directional,and the cells grew more than a single layer.In the HG group,as the intervention time prolonged,the number of CCSMCs decreased,and the shape of CCSMCs began from a slender bundle or vortex shape to a wider and more messy shape.The number of CCSMCs in each group of HG+JLD was not significantly reduced,and the cell morphology did not change significantly.2.Changes in phenotype protein Compared with NG group,the expression of α-SMA and calponin1 in HG group were significantly decreased(P<0.05);the expression of OPN was significantly increased(P<0.05).After high glucose was added to Jinlida,compared with HG group,the expression of ɑ-SMA and calponin1 increased in each group,and the expression of OPN was significantly decreased(P<0.05).The greater the concentration of Jinlida,the more obvious the reversal.The HC group did not have the above changes.The expression of caspase-3 protein in HG group was significantly increased compared with NG group(P<0.01),and the expression of bcl-2 protein was significantly decreased(P<0.01).Compared with HG group,Jin was compared with HG group.The expression of caspase-3 protein was significantly decreased in each group(P<0.05),and the expression of bcl-2 protein was significantly increased(P<0.01).Compared with NG group,the apoptosis rate of CCSMCs in HG group was significantly increased(P<0.01).The apoptosis rate of CCSMCs in Jinlida group was significantly lower than that in HG group(P<0.05).Compared with NG group,the expression of p-ERK1/2 protein in HG group was significantly up-regulated(P<0.01).The expression of p-ERK1/2 was decreased after adding ERK inhibitor PD98059(P<0.05).The expression of SMA and calponin1 was up-regulated;the expression of OPN was decreased.After intervention with Jinlida,the expression of p-ERK1/2 protein in each group was lower than that in HG group(P<0.05).Conclusion: High glucose may up-regulate the phosphorylation of ERK1/2 and induce CCSMCs to transform from contractile to synthetic and induce apoptosis of CCSMCs.Jinlida may improve the high glucose-induced changes by inhibiting the phosphorylation of ERK1/2. |
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