The Preventive And Therapeutic Effects Of Betaine On Early Injury In Db/db Mice With Diabetic Nephropathy

Diabetic nephropathy (DN) is a common and very harmful complication of the capillaryvessel in diabetes. The glomerulosclerosis is one of the most happened pathological changes,developing to renal failure in the end stage. So DN is one of the main reasons for the death ofpatients with diabetes.Betaine is one of water soluble quaternary ammonium alkaloids, widely found inanimals and plants. It can relieve stress, regulate osmotic pressure, increase appetite, reducefat; can be used as a methyl donor; also can be an alternative of methionine and cholinechloride. The hydrochloride of betaine can be used in the prevention and treatment ofachlorhydria, atherosclerosis sclerosis, liver disease, and rheumatism.Objective:to provide evidence for the evaluation on the medicinal value of betaine, thepreventive and therapeutic effects of betaine on the capillary vessel injury in db/db mice withdiabetic nephropathy were studied. The relevant mechanism of the effects was also explored.Method:According to the gender and body weight,55SPF db/db mice (10weeks) wererandomly divided into negative control group (physiological saline), positive control group(Zhibituo), low dose betaine group (100mg/kg), middle dose betaine group (200mg/kg), andhigh dose betaine group (400mg/kg). There were11mice in each group and the animalsreceived saline, Zhibituo, or betaine by intragastric administration.The mice were fasted for12hours after the first administration. The blood was collectedvia vena orbitalis posterior. The animals were sacrificed, and then the kidneys were taken foranalysis. The biochemical and immune indicators of the serum were detected. The kidne yparaffin sections were prepared and the pathological changes were analyzed basing on the HEstaining and oil red O staining.Results:1. The betaine and Zhibituo treatment groups compared with the negative control group(saline), the GLU, TG, TC, LDL, and BUN were significantly decreased (P <0.05); the ALTwas significantly decreased (P <0.01); body weight was also decreased (P <0.05). Thebetaine groups compared with Zhibituo group, no significant difference in GLU, TC, TG,LDL, ALT, and BUN values was observed (P>0.05).2. Compared with the negative control, the glomerular basement membrane in thebetaine and Zhibituo treatment group did not thicken; extracellular matrix, the glycoge nmaterial deposition and fiber content reduced; protein casts and inflammatory cell infil tration disappeared. Furthermore, the structure of renal tubule was gradually returning to normal, andthe mitochondria swelled and degenerated mildly.3. Compared with the negative control, TNF-α and TGF-β1in all betaine treatmentgroups decreased significantly (P <0.05). Compared with the Zhibituo gruop, TNF-α andTGF-β1inbetaine treatment groups also decreased significantly(P<0.05).Conclusions:1. Betaine has a hypoglycemic activity on db/db mice.2. Betaine has a protective effect on the kidney injury in db/db mice. It can significantlyimprove the renal pathological damage, and reduce the serum BUN levels in mice with renalinjury.3. Betaine has a lipid-lowering effect on db/db mice and can reduce serum TC and TGlevels.4. Betaine can reduce the serum TNF-α and TGF-β1levels in db/db mice, suggestingthat it may delay or inhibit the inflammatory process of the capillary vessel in diabeticnephropathy.